Drug Details

General Information of the Drug (ID: DR9021)
Name
5-fluorouracil
Synonyms
fluorouracil; 5-FU; Fluoroplex; Adrucil; Efudex; Carac; Fluracil; Fluoroblastin; 5-fluoropyrimidine-2,4(1H,3H)-dione; Kecimeton; Timazin; Carzonal; Efudix; Arumel; Fluril; Queroplex; Fluracilum; Ulup; 5-Fluoracil; Phthoruracil; Fluro Uracil; 5-Fluoro-2,4(1H,3H)-pyrimidinedione; Ftoruracil; Fluorouracilum; Efurix; Fluri; 51-21-8; 5 Fluorouracil; Effluderm (free base); 5-fluoro-1H-pyrimidine-2,4-dione; Fluorouracilo; Fluroblastin; Phtoruracil; 2,4-Dihydroxy-5-fluoropyrimidine; 2,4(1H,3H)-Pyrimidinedione, 5-fluoro-; Adrucil; Effluderm; Fluorouracile; Fluoruracil; Fluracedyl; Flurodex; Neofluor; Onkofluor; Ribofluor; Tetratogen; URF; Allergan Brand of Fluorouracil; Biosyn Brand of Fluorouracil; CSP Brand of Fluorouracil; Cinco FU; Dakota Brand of Fluorouracil; Dermatech Brand of Fluorouracil; Dermik Brandof Fluorouracil; Ferrer Brand of Fluorouracil; Fluoro Uracile ICN; Fluorouracil GRY; Fluorouracil Mononitrate; Fluorouracil Monopotassium Salt; Fluorouracil Monosodium Salt; Fluorouracil Potassium Salt; Fluorouracil Teva Brand; Fluorouracile Dakota; Fluorouracile [DCIT]; Fluorouracilo Ferrer Far; Gry Brand of Fluorouracil; Haemato Brand of Fluorouracil; Haemato fu; Hexal Brand of Fluorouracil; ICN Brand of Fluorouracil; Inhibits thymilidate synthetase; Medac Brand of Fluorouracil; Neocorp Brand of Fluorouracil; Onkoworks Brand of Fluorouracil; Ribosepharm Brand of Fluorouracil; Riemser Brand of Fluorouracil; Roche Brand of Fluorouracil; Teva Brand of Fluorouracil; F 6627; F0151; IN1335; U 8953; Adrucil (TN); Carac (TN); Dakota, Fluorouracile; Efudex (TN); Fluoro-Uracile ICN; Fluoro-uracile; Fluoro-uracilo; Fluoroplex (TN); Fluorouracil-GRY; Fluorouracilo [INN-Spanish]; Fluorouracilum [INN-Latin]; Haemato-fu; Ro 2-9757; U-8953; Ro-2-9757; Fluorouracil (JP15/USP/INN); Fluorouracil [USAN:INN:BAN:JAN]; 1-fluoro-1h-pyrimidine-2,4-dione; 2,4-Dioxo-5-fluoropryimidine; 2,4-Dioxo-5-fluoropyrimidine; 5 FU Lederle; 5 FU medac; 5 Fluorouracil biosyn; 5 HU Hexal; 5-FU (TN); 5-FU Lederle; 5-FU medac; 5-Faracil; 5-Fluor-2,4(1H,3H)-pyrimidindion; 5-Fluor-2,4(1H,3H)-pyrimidindion [Czech]; 5-Fluor-2,4-dihydroxypyrimidin; 5-Fluor-2,4-dihydroxypyrimidin [Czech]; 5-Fluor-2,4-pyrimidindiol; 5-Fluor-2,4-pyrimidindiol [Czech]; 5-Fluoracil [German]; 5-Fluoracyl; 5-Fluoro-2,4-pyrimidinedione; 5-Fluoropyrimidin-2,4-diol; 5-Fluoropyrimidine-2,4-dione; 5-Fluorouracil-biosyn; 5-Fluoruracil; 5-Fluoruracil [German]; 5-Ftouracyl; 5-HU Hexal; 5-fluoro uracil; 5FU
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Molecular Type
Small molecule
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C4H3FN2O2
PubChem CID
3385
Canonical SMILES
C1=C(C(=O)NC(=O)N1)F
InChI
1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
InChIKey
GHASVSINZRGABV-UHFFFAOYSA-N
CAS Number
CAS 51-21-8
ChEBI ID
CHEBI:46345
GDSC
5-Fluorouracil
TTD Drug ID
D05LEO
DrugBank ID
DB00544
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          6-shogaol      Acacia confusa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression ATG7  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
SW620 CVCL_0547 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 6-Shogaol enhances the anticancer effect of 5-fluorouracil via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.
          Alitretinoin      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Alitretinoin combined with topical 5-FU seems to be an interesting option in patients with DD, as it can allow a durable clinically complete remission with a good tolerance.
          Allicin      Allium fistulosum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
Up-regulation ROS generation
                    In-vitro Model SK-HEP-1 CVCL_0525 Hepatocellular carcinoma Homo sapiens
BEL-7402 CVCL_5492 Human hepatocellular carcinoma Homo sapiens
                    In-vivo Model Male athymic nude mice (4-6-week) were injected subcutaneously into left flank with 1*107 GFP-SK-Hep-1 cells.
                    Experimental
                    Result(s)		 Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway.
          Alpha solanine      Solanum tuberosum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
                    In-vitro Model EC9706 CVCL_E307 Esophageal squamous cell carcinoma Homo sapiens
KYSE-30 CVCL_1351 Esophageal squamous cell carcinoma Homo sapiens
                    In-vivo Model EC9706 cells (5*106), which were labeled with firefly luciferase, were subcutaneously inoculated into the armpit of the right forelimb of 6-week-old female BALB/c nude mice.
                    Experimental
                    Result(s)		 Alpha-solanine enhances the chemosensitivity of esophageal cancer cells by inducing microRNA 138 expression.
          Apigenin      Psilotum nudum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
Down-regulation Loss of mitochondrial membrane potential
                    In-vitro Model SK-HEP-1 CVCL_0525 Hepatocellular carcinoma Homo sapiens
BEL-7402 CVCL_5492 Human hepatocellular carcinoma Homo sapiens
                    In-vivo Model SK-Hep-1 cells (5*106 cells per mice) were suspended in 100 L of serum-free RPMI-1640 medium, then subcutaneously injected into the left flank of nude mice (Male, 4-6 weeks old).
                    Experimental
                    Result(s)		 Apigenin may potentiate the cytotoxicity of 5-FU in HCC via inhibition of ROS-mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 As2O3 in combination with 5-FU treatment caused up-regulation of DR5, caspase 3, caspase 8, and caspase 9, and down-regulation of BCL-2, but had no effect of DR4.
          Beta aescin      Aesculus chinensis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Mixtures of beta-aescin and 5-FU showed a synergistic effect on the 50% inhibitory effect when their ratio was 4:1 when compared with either agent alone.
          Betulinic Acid      Rubus alceifolius     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression Gli1  Molecule Info 
Pathway MAP
Down-regulation Expression GLI2  Molecule Info 
Pathway MAP
Down-regulation Expression IGF2  Molecule Info 
Pathway MAP
Down-regulation Expression PTCH1  Molecule Info 
Pathway MAP
                    In-vitro Model OVCAR-3 CVCL_0465 Ovarian serous adenocarcinoma Homo sapiens
Rh30 CVCL_0041 Alveolar rhabdomyosarcoma Homo sapiens
NIH 3T3 CVCL_0594 Healthy Mus musculus
                    Experimental
                    Result(s)		 Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells. Ovarian carcinoma cells on concurrent or 5-FU followed by BA treatment show increased Sub-G1 cell population, increased rate of cell apoptosis and morphological changes in mitochondrial membrane.
          Bufalin      Bufo gargarizans     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells.
          Capsaicin      Capsicum annuum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression ATG3  Molecule Info 
Pathway MAP
Down-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model QBC939 CVCL_6942 Cholangiocarcinoma Homo sapiens
SK-ChA-1 CVCL_6952 Cholangiocarcinoma Homo sapiens
Mz-ChA-1 CVCL_6932 Gallbladder carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Capsaicin enhances 5FU sensitivity of cholangiocarcinoma through the inhibition of 5FU-induced autophagy by activating the PI3K/AKT/mTOR pathway.
          Cardamonin      Alpinia zerumbet     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
Down-regulation Expression TCF7L2  Molecule Info 
Pathway MAP
                    In-vitro Model BGC-823 CVCL_3360 Gastric cancer Homo sapiens
                    In-vivo Model BGC-823/5-FU cells (5*106) were injected subcutaneously into the left flank of six-week-old BALB/c nude mice.
                    Experimental
                    Result(s)		 Cardamonin reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt/beta-catenin signal pathway.
          Chlorogenic acid      Imperata cylindrica     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases.
          Chrysin      Tripterygium wilfordii     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Expression CDK6  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression POLD1  Molecule Info 
Pathway MAP
                    In-vitro Model AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Chrysin potentiated the chemotherapeutic effect of 5-FU in gastric cancer AGS and AGS/FR cells via cell cycle arrest.
          Cucurbitacin E      Cucumic melo     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCC1  Molecule Info 
Pathway MAP
                    In-vitro Model DLD-1 CVCL_0248 Colon adenocarcinoma Homo sapiens
HCT 8 CVCL_2478 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
FHC CVCL_3688 Healthy Homo sapiens
                    In-vivo Model Six-week-old female nude mice received a subcutaneous injection of HCT-8/FU cells (1 * 106 suspended in 100 uL of PBS) on the right flank.
                    Experimental
                    Result(s)		 Cucurbitacin E chemosensitizes colorectal cancer cells via mitigating TFAP4/Wnt/Beta-Catenin signaling.
          Cucurbitacin I      Citrullus lanatus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model COLO 205 CVCL_0218 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Cucurbitacin I inhibits cell migration and invasion and enhances chemosensitivity in colon cancer.
          Elemene      Pogostemon cablin     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation c-RAF  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CYB5R2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3R1  Molecule Info 
Pathway MAP
                    In-vitro Model BT-549 CVCL_1092 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model MDA-MB-231 cells (5*106 cells in 100 uL of PBS) were subcutaneously injected to the left flank of femal nude mice.
                    Experimental
                    Result(s)		 Beta-Elemene enhances the chemotherapeutic effect of 5-Fluorouracil in triple-negative breast cancer via PI3K/AKT, RAF-MEK-ErK, and NF-KappaB signaling pathways.
          Ellagic acid      Lagerstroemia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
COLO 320DM CVCL_0219 Colon adenocarcinoma Homo sapiens
SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
LoVo CVCL_0399 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Ellagic acid synergistically potentiated chemosensitivity to 5-fluorouracil in colorectal cancer cells.
          Esculetin      Fraxinus chinensis     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Down-regulation Expression PCNA  Molecule Info 
Pathway MAP
Down-regulation Expression WNT3A  Molecule Info 
Pathway MAP
                    In-vitro Model Caco-2 CVCL_0025 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    In-vivo Model Animal models were constructed by injecting HCT-116 cells in the right flank of nude mice.
                    Experimental
                    Result(s)		 EST combined with 5-FU could increase the inhibitory effect of 5-FU on HCT-116 cells proliferation, migration and epithelial-mesenchymal transition.
          Eugenol      Coreopsis tinctoria     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Cell cycle arrest in S and G2/M phase
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Eugenol interacts synergistically with 5-fluorouracil against human cervical cancer, HeLa cell lines, by blocking the cell cycle and inducing apoptosis.
          Fisetin      Toxicodendron succedaneum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
Up-regulation Expression PRKAA1  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKalpha.
          Fluoroorotic acid      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.
          Fucoxanthin      Saccharina japonica     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction DNA damage
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT29 CVCL_A8EZ Colorectal adenocarcinoma Mus musculus
                    Experimental
                    Result(s)		 Since Phloroglucinol and Fucoxanthin alone reduced cancer cell line viability without an effect on normal cells and when in combination enhanced the cytotoxic effect of 5-Fu only in colon cancer cells.
          Gambogic acid      Garcinia morella     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PAEP  Molecule Info 
Pathway MAP
Down-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model BGC-823 CVCL_3360 Gastric cancer Homo sapiens
                    In-vivo Model Forty mice were inoculated sub cutaneously with injections of 1 * 106 BGC-823 cells/mouse.
                    Experimental
                    Result(s)		 GA attenuated 5-FU-induced apoptosis by modulating metabolic enzymes of 5-FU and the antigastric cancer effect of two drugs combination was much stronger than that of GA or 5-FU alone.
          Gamma linolenic acid      Gossypium hirsutum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 GLA has a synergistic effect with gemcitabine at concentrations that correspond to in vivo therapeutic doses. GLA with 5-FU is synergistic only at a tight range of high concentrations of 5-FU. GLA lacks toxic side effects and may be useful in combination with gemcitabine.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model MIA PaCa-2 cells (2*106 cells/100 L) were injected subcutaneously into the right flank of female nude mice aged 4-6 weeks.
                    Experimental
                    Result(s)		 Genistein potentiates the antitumor effect of 5-Fluorouracil by inducing apoptosis and autophagy in human pancreatic cancer cells.
          Geraniol      Rosa rugosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    In-vitro Model Caco-2 CVCL_0025 Colon adenocarcinoma Homo sapiens
SW620 CVCL_0547 Colon adenocarcinoma Homo sapiens
                    In-vivo Model Colorectal tumor TC118 obtained from patients was grafted by subcutaneous implantation of 15 mm3 tumor fragments into the scapular area of nude mice.
                    Experimental
                    Result(s)		 Geraniol modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts.
          Gossypol      Gossypium herbaceum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells.
          Honokiol      Magnolia officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model HSC-3 CVCL_1288 Tongue squamous cell carcinoma Homo sapiens
HSC-4 CVCL_1289 Tongue squamous cell carcinoma Homo sapiens
                    In-vivo Model A total of 2*106 HSC-3 cells were suspended in 100 uL serum-free DMEM and injected subcutaneously into the right flank of BALB/c nude mice to establish OSCC xenograft models.
                    Experimental
                    Result(s)		 HNK and 5-FU exert a synergistic therapeutic effect on OSCC by inducing apoptosis.
          Kaempferol      Equisetum hyemale     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 8 CVCL_2478 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Kaempferol has a synergistic effect with 5-FU by inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells via suppression of TS or attenuation of p-Akt activation.
          L-canavanine      Canavalia ensiformis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
                    In-vivo Model Male Fishcher rats weighing 150-175 g were used in this study.
                    Experimental
                    Result(s)		 Combination therapy offers a viable means of improving L-canavanine's intrinsic efficacy while decreasing the concentration of 5-FU required to produce the same cytotoxic effect.
          Licochalcone A      Glycyrrhiza inflata     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression IFI27  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MKN45 CVCL_0434 Gastric adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 LCA alone or in combination with 5-FU may have significant anticancer effects on gastric cancer cells.
          Luteolin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [36]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression DRAM1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vivo Model Solid tumors were induced by intramuscular inoculation of 0.2 mL of ascetic fluid, containing approximately 2.5*106 Ehrlich asites carcinoma cells, in the right thigh of the hind limb of each mouse.
                    Experimental
                    Result(s)		 Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma.
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model C-26 CVCL_XC68 Colorectal cancer Mus musculus
                    In-vivo Model BALB/c mice inoculated with C26 cells were used in this study.
                    Experimental
                    Result(s)		 The combination treatment of ME/5FU co-loaded hydrogels exhibited significant synergistic therapeutic efficacy in the BALB/c mouse model with transplanted subcutaneously tumor on the base of C26 cell line by inducing apoptosis and cell cycle arrest.
          Methylglyoxal      Saccharomyces cerevisiae     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [38]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CDK4  Molecule Info 
Pathway MAP
Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    In-vivo Model BALB/c mice model inoculated with 4T1. 1 * 106 4T1 cells were subcutaneously injected into the mammary fat pad region of BALB/c mice to develop solid tumors.
                    Experimental
                    Result(s)		 MG could be a potential candidate for combination therapy to reduce the toxicity burden of 5-FU without any toxic impact on host cells.
          Oroxylin A      Oroxylum indicum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [39]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Murine hepatoma 22 (H22) cells were diluted with icy 0.9% saline and inoculated subcutaneously at right axilla of mice (5*106 viable cells/mL).
                    Experimental
                    Result(s)		 The anti-hepatocellular carcinoma effects in vitro and in vivo of 5-FU and oroxylin A combinations were synergistic and oroxylin A increased the sensitivity of HepG2 cells to 5-FU by modulating the metabolic enzymes of 5-FU and apoptotic-related proteins.
          Pentagalloylglucose      Paeonia suffruticosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [40]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression C1D  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNE1  Molecule Info 
Pathway MAP
Up-regulation Expression IFI27  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination significantly downregulated MDR1 and LRP1, suggesting the potential to reverse the resistance to 5-FU.
          Procyanidin      Cinnamomum camphora     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [41]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Caco-2 CVCL_0025 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Procyanidin enhances the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells.
          Pterostilbene      Vitis vinifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [42]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression FOXO1  Molecule Info 
Pathway MAP
Up-regulation Expression IFI27  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model Caco-2 CVCL_0025 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Pterostilbine sensitizes colon cancer cells to 5-fluorouracil cytotoxicity.
          Quercetin      Averrhoa carambola     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [43]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model Co-115 CVCL_D102 Colon adenocarcinoma Homo sapiens
HCT 15 CVCL_0292 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [44]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model TE-1 CVCL_1759 Esophageal squamous cell carcinoma Homo sapiens
A-431 CVCL_0037 Skin squamous cell carcinoma Homo sapiens
                    In-vivo Model The topical use of 7, 12-dimethylbenz[a]anthracene (DMBA) in acetone (150 mg/mouse) served as a tumor initiator in swiss albino mice.
                    Experimental
                    Result(s)		 Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis.
          Rutin      Fagopyrum esculentum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [45]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application.
          Salicylic acid      Salix abscondita     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [46]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Medical record review
                    Experimental
                    Result(s)		 It was observed that the twice-daily application of topical fluorouracil and salicylic acid is a safe and effective treatment for verruca plantaris.
          Scutellarin      Scutellaria indica     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [47]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP6  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Scutellarin sensitizes 5FU-evoked colon cancer cell apoptosis through enhanced caspase-6 activation.
          Streptozocin      Streptomyces achromogenes     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [48]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Medical records
                    Experimental
                    Result(s)		 The combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response and has an acceptable toxicity profile.
          Sulforaphane      Brassica oleracea     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [49]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Sulforaphane and 5-fluorouracil have been shown to interact synergistically in the breast cancerMDA-MB-231 cell line, resulting in a significant reduction of the number of live cells compared to alone treatments.
          Tangeretin      Citrus reticulata     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [50]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BID  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation TP53  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HCT 15 CVCL_0292 Colon adenocarcinoma Homo sapiens
KM12-C CVCL_9547 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of TAN and 5-FU significantly accelerates apoptosis via JNK mediated pathway.
          Thymoquinone      Nigella sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [51]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
Up-regulation Expression DKK1  Molecule Info 
Pathway MAP
Up-regulation Expression GPX1  Molecule Info 
Pathway MAP
Down-regulation Expression NOS2  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression SMAD4  Molecule Info 
Pathway MAP
Up-regulation Expression TGFB1  Molecule Info 
Pathway MAP
Up-regulation Expression TGFBR2  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
Down-regulation Expression WNT1  Molecule Info 
Pathway MAP
                    In-vivo Model For induction of colorectal tumorigenesis, AOM was dissolved in normal saline and injected subcutaneously at a dose of 15 mg/kg, once weekly for 2 weeks.
                    Experimental
                    Result(s)		 Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats.
          Tretinoin      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [52]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model A case report
                    Experimental
                    Result(s)		 Combination of imiquimod, 5-fluorouracil, and tretinoin is an effective viable treatment modality for treating melanoma in situ during a pandemic with telemedicine.
          Triamcinolone      Cladosporium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [53]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression COL1A1  Molecule Info 
Pathway MAP
Down-regulation Expression TGFB1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2 phase
                    In-vitro Model Keloid fibroblasts Healthy Homo sapiens
                    Experimental
                    Result(s)		 Combination of TA and 5-FU showed synergistic interation in regulating the biological behaviour of keloid fibroblasts in vitro.
          Triptolide      Tripterygium hypoglaucum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [54]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
                    In-vitro Model NCI-H630 CVCL_1572 Colorectal cancer Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 PG490 strongly enhanced the cytotoxicity of 5-FU. PG490 also simultaneously induced ROS and inhibited NF-KappaB activity and significantly enhanced the cytotoxic effect of 5-FU in three CRC cell lines in vitro.
          Ulinastatin      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [55]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression WNT3A  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 UTI enhanced the 5-FU sensitivity of HCC cells by attenuating their stemness via inhibiting Wnt/Beta-catenin signaling.
          Wogonin      Scutellaria amoena     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [56]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation IKKA  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Nude mice were inoculated subcutaneously with injections of 1*107 SMMC-7721 cells/mouse at the right axilla.
                    Experimental
                    Result(s)		 Wogonin enhances 5-FU cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway.
          Atractylodes macrocephala + Panax ginseng total saponins     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [63]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model The mice were administered with AMO, PGS and AP respectively for 11 days, and intraperitoneally injected with 5-FU for 6 days since the 3rd day of the experiment.
                    Experimental
                    Result(s)		 Combination of AMO and PGS, not AMO or PGS alone, significantly ameliorated diarrhea, inhibited intestinal pathology, and modulated gut microbial structure in 5-FU induced mice.
          Cinobufotalin + Paclitaxel     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [64]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model UM-SCC-5 CVCL_7762 Laryngeal squamous cell carcinoma Homo sapiens
FaDu CVCL_1218 Squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 TPF regimen combining cinobufotalin suppressed proliferation and promoted apoptosis synergistically in hypopharyngeal squamous cell carcinoma and laryngeal squamous cell carcinoma cells.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Crocin      Crocus sativus     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [57]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model CT26 CVCL_7254 Mouse colon adenocarcinoma Mus musculus
                    In-vivo Model Eight-week old female C57BL/6 mice were used in this study.
                    Experimental
                    Result(s)		 Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer.
          Streptozocin      Streptomyces achromogenes     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [58]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.
    γ. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          Andrographolide      Astragalus membranaceus     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [59]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression DKK1  Molecule Info 
Pathway MAP
                    Experimental
                    Result(s)		 Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [60]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression HSP20  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cell cycle arrest in G0/G1 phase
                    In-vitro Model HCT 8 CVCL_2478 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Down-regulation of P-gp and HSP-27, two multidrug resistance related factors, may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU.
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [61]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression TFAP2A  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
                    In-vivo Model Exponentially growing SCG7901/FU cells (5*106) were injected subcutaneously into the dorsum of female BALB/c nude mice.
                    Experimental
                    Result(s)		 Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer.
          Lactobacillus plantarum      Lactiplantibacillus plantarum     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [62]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Down-regulation cAMP content
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 GABA-producing L. plantarum is promising as an adjuvant treatment for 5-FU-resistant CRC, and its intervention in neurobiological signaling imply new possibilities for chemoprevention and the treatment of colon cancer-related diseases.
Target and Pathway
Target(s) Thymidylate synthase (TYMS)  Molecule Info  [65]
References
Reference 1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
Reference 2 6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions. BMC Complement Med Ther. 2020 May 11;20(1):141.
Reference 3 Combination of alitretinoin and topical 5-fluorouracil in Darier disease. JAAD Case Rep. 2018 Dec 11;5(1):75-77.
Reference 4 Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway. J Pharmacol Sci. 2016 Aug;131(4):233-40.
Reference 5 Alpha-solanine enhances the chemosensitivity of esophageal cancer cells by inducing microRNA?138 expression. Oncol Rep. 2018 Mar;39(3):1163-1172.
Reference 6 5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential mediated apoptosis in hepatocellular carcinoma. Clin Exp Pharmacol Physiol. 2015 Feb;42(2):146-53.
Reference 7 Arsenic trioxide reduces chemo-resistance to 5-fluorouracil and cisplatin in HBx-HepG2 cells via complex mechanisms. Cancer Cell Int. 2015 Dec 12;15:116.
Reference 8 Synergistic effects of beta-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells. Phytomedicine. 2010 Jul;17(8-9):575-80.
Reference 9 Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells. Int J Clin Exp Pathol. 2015 Jan 1;8(1):252-9.
Reference 10 Bufalin and 5-fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncol Lett. 2018 May;15(5):8019-8026.
Reference 11 Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy. PLoS One. 2015 May 1;10(5):e0121538.
Reference 12 Cardamonin, a natural chalcone, reduces 5-fluorouracil resistance of gastric cancer cells through targeting Wnt/beta-catenin signal pathway. Invest New Drugs. 2020 Apr;38(2):329-339.
Reference 13 Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs. 2015 Jun;26(5):540-6.
Reference 14 Potentiating activities of chrysin in the therapeutic efficacy of 5-fluorouracil in gastric cancer cells. Oncol Lett. 2021 Jan;21(1):24.
Reference 15 Cucurbitacin E Chemosensitizes Colorectal Cancer Cells via Mitigating TFAP4/Wnt/Beta-Catenin Signaling. J Agric Food Chem. 2020 Nov 18.
Reference 16 Cucurbitacin I inhibits cell migration and invasion and enhances chemosensitivity in colon cancer. Oncol Rep. 2015 Apr;33(4):1867-71.
Reference 17 beta-Elemene Enhances the Chemotherapeutic Effect of 5-Fluorouracil in Triple-Negative Breast Cancer via PI3K/AKT, RAF-MEK-ErK, and NF-kappaB Signaling Pathways. Onco Targets Ther. 2020 Jun 9;13:5207-5222.
Reference 18 Effects of ellagic acid on chemosensitivity to 5-fluorouracil in colorectal carcinoma cells. Anticancer Res. 2012 Oct;32(10):4413-8.
Reference 19 Esculetin enhances the inhibitory effect of 5-Fluorouracil on the proliferation, migration and epithelial-mesenchymal transition of colorectal cancer. Cancer Biomark. 2019;24(2):231-240.
Reference 20 Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line. Phytomedicine. 2013 Jan 15;20(2):151-8.
Reference 21 Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer. Int J Cancer. 2019 Dec 1;145(11):3022-3032.
Reference 22 Efficacy and safety of oxaliplatin, 5-Fluorouracil, and folinic Acid combination chemotherapy as first-line treatment in metastatic or recurrent gastric cancer. Cancer Res Treat. 2011 Sep;43(3):154-9.
Reference 23 Treatment of advanced digestive non-colon cancer with a weekly 24-h infusion of high-dose 5-fluorouracil modulated by folinic acid and cisplatin: an easy-to-use and well-tolerated combination. Anticancer Drugs. 2004 Aug;15(7):725-8.
Reference 24 Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. Anticancer Drugs. 2007 Aug;18(7):793-800.
Reference 25 Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid. Biochem Pharmacol. 2001 Apr 1;61(7):867-76.
Reference 26 Anticancer effects of seaweed compounds fucoxanthin and phloroglucinol, alone and in combination with 5-fluorouracil in colon cells. J Toxicol Environ Health A. 2017;80(13-15):776-787.
Reference 27 Synergistic effect of 5-fluorouracil with gambogic acid on BGC-823 human gastric carcinoma. Toxicology. 2009 Feb 4;256(1-2):135-40.
Reference 28 Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines. Pancreatology. 2003;3(5):367-73; discussion 373-4.
Reference 29 Genistein potentiates the antitumor effect of 5-Fluorouracil by inducing apoptosis and autophagy in human pancreatic cancer cells. Anticancer Res. 2014 Sep;34(9):4685-92.
Reference 30 Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts. Cancer Lett. 2004 Nov 8;215(1):53-9.
Reference 31 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86.
Reference 32 Synergistic effect of honokiol and 5-fluorouracil on apoptosis of oral squamous cell carcinoma cells. J Oral Pathol Med. 2017 Mar;46(3):201-207.
Reference 33 Synergistic effect of kaempferol and 5?fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway. Mol Med Rep. 2019 Jul;20(1):728-734.
Reference 34 Combination therapy with 5-fluorouracil and L-canavanine: in vitro and in vivo studies. Anticancer Drugs. 1995 Aug;6(4):586-93.
Reference 35 Antitumor effects and the underlying mechanism of licochalcone A combined with 5-fluorouracil in gastric cancer cells. Oncol Lett. 2017 Mar;13(3):1695-1701.
Reference 36 Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma: Realistic role of P53; a guardian fights in a cellular battle. Chem Biol Interact. 2019 Sep 1;310:108740.
Reference 37 Synergistic therapeutic effects of Schiff's base cross-linked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model. Biomaterials. 2016 Jan;75:148-162.
Reference 38 Methylglyoxal in combination with 5-Fluorouracil elicits improved chemosensitivity in breast cancer through apoptosis and cell cycle inhibition. Biomed Pharmacother. 2019 Jun;114:108855.
Reference 39 Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human hepatocellular carcinoma and on H22 transplanted mice. Cancer Chemother Pharmacol. 2010 Feb;65(3):481-9.
Reference 40 Inhibitory effects and molecular mechanisms of pentagalloyl glucose in combination with 5-FU on aggressive phenotypes of HepG2 cells. Nat Prod Res. 2021 Mar;35(5):815-818.
Reference 41 Low molecular weight procyanidins from grape seeds enhance the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells. PLoS One. 2014 Jun 6;9(6):e98921.
Reference 42 Pterostilbine, an active component of blueberries, sensitizes colon cancer cells to 5-fluorouracil cytotoxicity. Sci Rep. 2015 Oct 16;5:15239.
Reference 43 Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation. Cancer Chemother Pharmacol. 2011 Dec;68(6):1449-57.
Reference 44 Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis. Exp Biol Med (Maywood). 2015 Dec;240(12):1672-81.
Reference 45 Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression. Adv Pharm Bull. 2019 Aug;9(3):462-469.
Reference 46 Treatment of verruca plantaris with a combination of topical fluorouracil and salicylic acid. J Am Podiatr Med Assoc. Jul-Aug 2005;95(4):366-9.
Reference 47 Scutellarin sensitizes drug-evoked colon cancer cell apoptosis through enhanced caspase-6 activation. Anticancer Res. 2009 Aug;29(8):3043-7.
Reference 48 Streptozocin and 5-Fluorouracil for the Treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity. Neuroendocrinology. 2016;103(3-4):345-53.
Reference 49 Autophagic cell death and premature senescence: New mechanism of 5-fluorouracil and sulforaphane synergistic anticancer effect in MDA-MB-231 triple negative breast cancer cell line. Food Chem Toxicol. 2018 Jan;111:1-8.
Reference 50 Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cell. Food Chem Toxicol. 2020 Sep;143:111529.
Reference 51 Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats. Drug Des Devel Ther. 2016 Jul 11;10:2239-53.
Reference 52 Treating Melanoma in Situ During a Pandemic with Telemedicine and a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin. Dermatol Ther (Heidelb). 2021 Feb;11(1):307-314.
Reference 53 A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro. J Plast Reconstr Aesthet Surg. 2013 Sep;66(9):e251-9.
Reference 54 Triptolide simultaneously induces reactive oxygen species, inhibits NF-kappaB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines. Cancer Lett. 2010 May 28;291(2):200-8.
Reference 55 The combination of ulinastatin and 5-fluorouracil synergistically inhibits hepatocellular carcinoma growth. J Int Med Res. 2020 Mar;48(3):300060520909776.
Reference 56 Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway. Biochem Cell Biol. 2013 Aug;91(4):221-9.
Reference 57 Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem. 2018 Dec;119(12):10250-10261.
Reference 58 Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases. Ann Surg Oncol. 2018 Jun;25(6):1709-1715.
Reference 59 Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer. Carcinogenesis. 2021 Jun 21;42(6):814-825.
Reference 60 Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein. Chin J Integr Med. 2019 Jun;25(6):416-424.
Reference 61 Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer. Oncotarget. 2017 Sep 6;8(47):82842-82853.
Reference 62 GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABA B receptor signaling. J Microbiol. 2021 Feb;59(2):202-216.
Reference 63 Ameliorative effect of Atractylodes macrocephala essential oil combined with Panax ginseng total saponins on 5-fluorouracil induced diarrhea is associated with gut microbial modulation. J Ethnopharmacol. 2019 Jun 28;238:111887.
Reference 64 Combination of TPF regimen and cinobufotalin inhibits proliferation and induces apoptosis in human hypopharyngeal and laryngeal squamous cell carcinoma cells. Onco Targets Ther. 2018 Dec 31;12:341-348.
Reference 65 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
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