Natural Product (NP) Details

General Information of the NP (ID: NP6047)
Name
Metformin
Synonyms
1,1-Dimethylbiguanide; N,N-dimethylimidodicarbonimidic diamide; Metformine; Metiguanide; Dimethylbiguanide; Haurymelin; Fluamine; Flumamine; Gliguanid; Diabex; Melbin; N,N-Dimethylbiguanide; Glumetza; Imidodicarbonimidic diamide, N,N-dimethyl-; N1,N1-Dimethylbiguanide; DMGG; NNDG; N,N-Dimethyldiguanide; 1,1-Dimethyl biguanide; LA-6023; BIGUANIDE, 1,1-DIMETHYL-; 3-(diaminomethylidene)-1,1-dimethylguanidine; Fortamet; UNII-9100L32L2N; CHEMBL1431; CHEBI:6801; Glifage; Islotin; Siofor; Dimethyldiguanide; Diaformin; 9100L32L2N; Metformina [DCIT]; Metforminum; Metformina; Metformina [Spanish]; Metformine [INN-French]; Metforminum [INN-Latin]; Metformin [USAN:INN:BAN]; MLS000028493; [14C]metformin; [14C]-metformin; C4H11N5; 657M249; Metformin (USAN/INN); NCGC00016564-01; SMR000058277; EINECS 211-517-8; CAS-1115-70-4; Dianben; Obimet; Dimethylbiguanid; Metformin base; CCRIS 9321; N-dimethylbiguanide; DMBG; Glucophage (Salt/Mix); n',n'-dimethylbiguanide; Imidodicarbonimidic diamide-, N,N-dimethyl-; Prestwick0_000004; Prestwick1_000004; Prestwick2_000004; Prestwick3_000004; DSSTox_CID_3270; N,N-Dimethylguanylguanidin; SCHEMBL8944; DSSTox_RID_76950; DSSTox_GSID_23270; BSPBio_000007; BSPBio_002314; KBioGR_002310; KBioSS_002312; cid_14219; LA 6023 (Salt/Mix); BIDD:GT0697; SPBio_001928; BPBio1_000009; GTPL4503; GTPL4779; SCHEMBL9913821; DTXSID2023270; SCHEMBL10276396; BDBM57047; KBio2_002310; KBio2_004878; KBio2_007446; KBio3_002790; cMAP_000016; HMS2089D19; HY-B0627; Tox21_302370; BBL012337; BDBM50229665; HSCI1_000295; s5958; STK011633; STL483693; STL484070; ZINC12859773; AKOS000121065; AKOS005206848; AKOS015966566; CCG-102605; DB00331; MCULE-7393156510; 3-carbamimidoyl-1,1-dimethyl-guanidine; AC-32484; AS-65365; CAS-657-24-9; K070; SBI-0206876.P001; 1-carbamimidamido-N,N-dimethylmethanimidamide; CS-0009563; FT-0628266; A19551; C07151; D04966; Q19484; (E)-3-[Amino(dimethylamino)methylidene]guanidine; 1-[(E)-amino(dimethylamino)methylidene]guanidine; W-109589;
    Click to Show/Hide
Species Origin Galega officinalis ...     Click to Show/Hide
Galega officinalis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Galega
Species: Galega officinalis
Disease Type 2 diabetes mellitus [ICD-11: 5A11] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C4H11N5
PubChem CID
4091
Canonical SMILES
CN(C)C(=N)N=C(N)N
InChI
1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
InChIKey
XZWYZXLIPXDOLR-UHFFFAOYSA-N
CAS Number
CAS 657-24-9
TTD Drug ID
D0D8RC
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Gemigliptin      Acute diabete complication     Click to Show/Hide the Molecular Data of This Drug
                 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		 Down-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
Down-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model TPC-1 CVCL_6298 Thyroid gland papillary carcinoma Homo sapiens
SW1736 CVCL_3883 Thyroid gland anaplastic carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells.
          6-benzylthioinosine      Acute myeloid leukemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
MOLM-14 CVCL_7916 Adult acute myeloid leukemia Homo sapiens
OCI-AML-3 CVCL_1844 Adult acute myeloid leukemia Homo sapiens
NOMO-1 CVCL_1609 Adult acute monocytic leukemia Homo sapiens
THP-1 CVCL_0006 Childhood acute monocytic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression.
          Nelfinavir      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
SiHa CVCL_0032 Cervical squamous cell carcinoma Homo sapiens
Ca Ski CVCL_1100 Cervical squamous cell carcinoma Homo sapiens
                    In-vivo Model Cervical cancer cell xenograft in vivo in nude mice were used in this study.
                    Experimental
                    Result(s)		 Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.
          Valproic acid      Epilepsy/seizure     Click to Show/Hide the Molecular Data of This Drug
                 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 TP53  Molecule Info 
Pathway MAP
                    In-vitro Model LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 MET + VPA induced a significant decrease in proliferation and an increase in apoptosis in tumor cells.
          Simvastatin      Hyper-lipoproteinaemia     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 D12 CVCL_4Y40 Prostate carcinoma Homo sapiens
LNCaP C4-2B5 CVCL_4788 Prostate carcinoma Homo sapiens
LNCaP C4-2B4 CVCL_4787 Prostate carcinoma Homo sapiens
LNCaP C4-2B3 CVCL_4786 Prostate carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model Male NCr-nu/nu mice were used in this study.
                    Experimental
                    Result(s)		 Combination of simvastatin and metformin, within pharmacologic dose range (500 nmol/L to 4 umol/L simvastatin and 250 umol/L to 2 mmol/L metformin), significantly and synergistically reduces C4-2B3/B4 CRPC cell viability and metastatic properties, with minimal adverse effects on normal prostate epithelial cells.
          C1632      Lip/oral cavity/pharynx neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 HMGA2  Molecule Info 
Pathway MAP
Down-regulation Expression Lin-28A  Molecule Info 
Pathway MAP
                    In-vitro Model SCC-9 CVCL_1685 Tongue squamous cell carcinoma Homo sapiens
CAL-27 CVCL_1107 Tongue squamous cell carcinoma Homo sapiens
                    In-vivo Model Each nude mouse was subcutaneously injected in the flank back skin with 200 uL of serum-free DMEM containing 8 * 106 CAL27 cells.
                    Experimental
                    Result(s)		 C1632 and metformin exerts synergistic anti-tumor effects in OSCC cell lines SCC9 and CAL27, and also inhibits xenograft tumor growth in vivo.
          Gefitinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Expression c-RAF  Molecule Info 
Pathway MAP
Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model Calu-3 CVCL_0609 Lung adenocarcinoma Homo sapiens
GLC-82 CVCL_3371 Non-small cell lung cancer Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin and gefitinib are synergistic in LKB1 wild-type NSCLC cells.
          Torin 2      Mature T-cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 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 mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model KPC3 CVCL_A9ZK Mouse pancreatic neoplasm Mus musculus
                    In-vivo Model To establish the xenograft model, the transplanted KPC adenocarcinoma cell lines (5 * 103 cells) in 30 uL PBS were injected in the gastric lobe of the pancreas of C57BL/6 albino mice.
                    Experimental
                    Result(s)		 The combination of mTOR dual inhibition by Torin 2 and metformin is associated with an altered metabolomic profile and a significant reduction in pancreatic tumor burden compared with single-agent therapy, and it is better tolerated.
          Dacarbazine      Melanoma     Click to Show/Hide the Molecular Data of This Drug
                 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 JNK2  Molecule Info 
Pathway MAP
                    In-vitro Model Raji CVCL_0511 EBV-related Burkitt lymphoma Homo sapiens
Ramos CVCL_0597 Burkitt lymphoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin showed synergistic cytotoxic effects in combination with dacarbazine, reduced cell viability, and increased apoptosis in Raji and Ramos lymphoma cells in comparison with the use of each drug alone.
          Trametinib      Melanoma     Click to Show/Hide the Molecular Data of This Drug
                 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		 Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model D04 CVCL_H604 Melanoma Homo sapiens
MM415 CVCL_2608 Melanoma Homo sapiens
MM485 CVCL_2610 Melanoma Homo sapiens
SK-MEL-2 CVCL_0069 Melanoma Homo sapiens
MaMel30I CVCL_A165 Melanoma Homo sapiens
MaMel27II CVCL_A163 Melanoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin and trametinib combinations are effective in preclinical models and may be a possible option for treatment of NRAS mutant cancers.
          Olaparib      Ovarian cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model UWB1.289 CVCL_B079 BRCA1 syndrome Homo sapiens
UWB1.289+BRCA1 CVCL_B078 BRCA1 syndrome Homo sapiens
SK-OV-3 CVCL_0532 Ovarian serous cystadenocarcinoma Homo sapiens
OVCAR-3 CVCL_0465 Ovarian serous adenocarcinoma Homo sapiens
A2780 CVCL_0134 Ovarian endometrioid adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining PARP inhibitors with metformin enhances its anti-proliferative activity in BRCA mutant ovarian cancer cells.
          Pemetrexed      Pleural mesothelioma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Metformin synergistic pemetrexed suppresses non-small-cell lung cancer cell proliferation and invasion in vitro.
          Everolimus      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model HCC1428 CVCL_1252 Breast adenocarcinoma Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
BT-549 CVCL_1092 Invasive breast carcinoma Homo sapiens
                    In-vivo Model HCC1428 cells (1.0*106) were injected subcutaneously into the abdominal mammary fat pads of female BALB/c-nu mice.
                    Experimental
                    Result(s)		 Metformin displays anti-myeloma activity and synergistic effect with dexamethasone in in vitro and in vivo xenograft models.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model HTh74 CVCL_6288 Thyroid gland anaplastic carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Sorafenib and metformin synergistically decreased the proliferation of ATC cell lines and the outgrowth of their derived cancer stem cells.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    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.
          PFK15      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 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 Expression PFKFB3  Molecule Info 
Pathway MAP
                    In-vitro Model RPMI-8226 CVCL_0014 Plasma cell myeloma Homo sapiens
OPM-2 CVCL_1625 Plasma cell myeloma Homo sapiens
                    Experimental
                    Result(s)		 The synergistic effect of PFK15 with metformin exerts anti-myeloma activity via PFKFB3.
          Liraglutide      Type 2 diabetes mellitus     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model HUVEC-C CVCL_2959 Healthy Homo sapiens
                    In-vivo Model High fat diet (HFD)-fed ApoE-/- mice were used in this study.
                    Experimental
                    Result(s)		 Combination of metformin and liraglutide has synergistic protective effects on endothelial function.
          Glibenclamide      Acute diabete complication     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    In-vivo Model Clinical Trial
                    Experimental
                    Result(s)		 Combination of glibenclamide-metformin should be considered in patients, without renal or cardiovascular impairment, who are not controlled on monotherapy alone.
          Atorvastatin      Cardiovascular disease     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Empagliflozin      Diabetes mellitus     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Experimental
                    Result(s)		 Initial combinations of empagliflozin + metformin for 24 weeks significantly reduced HbA1c versus empagliflozin once daily and metformin twice daily, without increased hypoglycemia, reduced weight versus metformin twice daily, and were well tolerated.
          Fluvastatin      Hyper-lipoproteinaemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Lovastatin      Hyper-lipoproteinaemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Pravastatin      Hyper-lipoproteinaemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Rosuvastatin      Hyper-lipoproteinaemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
          Erlotinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 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)		 Metformin and EGFR-TKI have a synergistic effect in the treatment of DM2 NSCLC patients harboring EGFR-activating mutations.
          Rapamycin      Multiple myeloma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model The in vovo experiment was carried out with male Wistar rats.
                    Experimental
                    Result(s)		 Cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response.
          2-deoxy-D-glucose      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model VOA1056 CVCL_V536 Adenocarcinoma Homo sapiens
VOA1312 CVCL_V538 Adenocarcinoma Homo sapiens
VOA5646 CVCL_VQ39 Adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 2-DG significantly inhibited glycolysis in all LGSOC lines and combination with metformin showed synergistic inhibitory effect.
          Ertugliflozin      Type 2 diabetes mellitus     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 The fixed-dose combination of ertugliflozin with metformin is an effective combination that is conveniently administered and may improve medication adherence and persistence.
          GSK2041706      Type 2 diabetes mellitus     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vivo Model Diet-induced obese (DIO) mouse models were used in this study.
                    Experimental
                    Result(s)		 The combination of GSK2041706 with metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels compared with their monotherapy groups.
          Pioglitazone + Exenatide     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Experimental
                    Result(s)		 Metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.
Target and Pathway
Target(s) Mannose receptor (MRC1)  Molecule Info  [28]
References
Reference 1 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 212614
Reference 2 Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells. Endocrine. 2018 Feb;59(2):383-394.
Reference 3 Synergistic cell death in FLT3-ITD positive acute myeloid leukemia by combined treatment with metformin and 6-benzylthioinosine. Leuk Res. 2016 Nov;50:132-140.
Reference 4 Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice. Sci Rep. 2017 Mar 2;7:43373.
Reference 5 The Combination of Metformin and Valproic Acid Induces Synergistic Apoptosis in the Presence of p53 and Androgen Signaling in Prostate Cancer. Mol Cancer Ther. 2017 Dec;16(12):2689-2700.
Reference 6 Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014 Oct;13(10):2288-302.
Reference 7 In vitro and in vivo synergistic anti-tumor effect of LIN28 inhibitor and metformin in oral squamous cell carcinoma. Eur J Pharmacol. 2021 Jan 15;891:173757.
Reference 8 Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3508-19.
Reference 9 The Synergistic Effect of an ATP-Competitive Inhibitor of mTOR and Metformin on Pancreatic Tumor Growth. Curr Dev Nutr. 2020 Aug 10;4(9):nzaa131.
Reference 10 The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells. Curr Mol Pharmacol. 2018;11(4):336-342.
Reference 11 Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer. Oncotarget. 2015 Jan 20;6(2):969-78.
Reference 12 Preclinical evaluation of olaparib and metformin combination in BRCA1 wildtype ovarian cancer. Gynecol Oncol. 2016 Aug;142(2):323-31.
Reference 13 Metformin synergistic pemetrexed suppresses non-small-cell lung cancer cell proliferation and invasion in vitro. Cancer Med. 2017 Aug;6(8):1965-1975.
Reference 14 Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells. Oncol Res. 2014;22(4):193-201.
Reference 15 Synergistic anti-proliferative effect of metformin and sorafenib on growth of anaplastic thyroid cancer cells and their stem cells. Oncol Rep. 2015 Apr;33(4):1994-2000.
Reference 16 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 17 The synergistic effect of PFK15 with metformin exerts anti-myeloma activity via PFKFB3. Biochem Biophys Res Commun. 2019 Jul 23;515(2):332-338.
Reference 18 Synergistic effects of metformin with liraglutide against endothelial dysfunction through GLP-1 receptor and PKA signalling pathway. Sci Rep. 2017 Feb 1;7:41085.
Reference 19 Combination of glibenclamide-metformin HCl for the treatment of type 2 diabetes mellitus. Expert Opin Pharmacother. 2012 Dec;13(17):2545-54.
Reference 20 Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies. J Pharm Pract. 2017 Apr;30(2):185-194.
Reference 21 Initial Combination of Empagliflozin and Metformin in Patients With Type 2 Diabetes. Diabetes Care. 2016 Oct;39(10):1718-28.
Reference 22 Synergistic effects of metformin in combination with EGFR-TKI in the treatment of patients with advanced non-small cell lung cancer and type 2 diabetes. Cancer Lett. 2015 Dec 1;369(1):97-102.
Reference 23 Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes. Rejuvenation Res. 2017 Oct;20(5):420-429.
Reference 24 Synergistic effect of MEK inhibitor and metformin combination in low grade serous ovarian cancer. Gynecol Oncol. 2017 Aug;146(2):319-326.
Reference 25 Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2019 Mar;14(2):75-83.
Reference 26 Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice. J Pharmacol Exp Ther. 2015 Jun;353(3):496-504.
Reference 27 Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015 Mar;17(3):268-75.
Reference 28 A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. March 2020
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link