Natural Product (NP) Details

General Information of the NP (ID: NP5424)
Name
Flavopiridol
Synonyms
FLAVO; Alvocidib [INN]; Flavopiridol hydrochloride; L 868275; HMR-1275; L-868275; L86-8275; HMR-1275, Alvocidib, L868275, Flavopiridol; (-)-cis-5,7-Dihydroxy-2-(2-chlorophenyl)-8-(4-(3-hydroxy-1-methyl)piperidinyl)-4H-1-benzopyran-4-one; 2-(2-CHLORO-PHENYL)-5,7-DIHYDROXY-8-(3-HYDROXY-1-METHYL-PIPERIDIN-4-YL)-4H-BENZOPYRAN-4-ONE; 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one
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Species Origin Dysoxylum binectariferum ...     Click to Show/Hide
Dysoxylum binectariferum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Meliaceae
Genus: Dysoxylum
Species: Dysoxylum binectariferum
Disease Chronic lymphocytic leukaemia [ICD-11: 2A82] Discontinued in Phase 3 [1]
Structure
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2D MOL

3D MOL

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Formula
C21H20ClNO5
PubChem CID
5287969
Canonical SMILES
CN1CCC(C(C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O
InChI
1S/C21H20ClNO5/c1-23-7-6-12(17(27)10-23)19-14(24)8-15(25)20-16(26)9-18(28-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,17,24-25,27H,6-7,10H2,1H3/t12-,17+/m0/s1
InChIKey
BIIVYFLTOXDAOV-YVEFUNNKSA-N
CAS Number
CAS 146426-40-6
Herb ID
HBIN026567
TTD Drug ID
D0LF1U
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Trastuzumab      Breast 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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-453 CVCL_0418 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Synergy between flavopiridol and trastuzumab can result from enhanced apoptosis, and that combination effects on EGFR expression are involved in the interaction.
          Venetoclax      Chronic lymphocytic leukaemia     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 BCL2L11  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H929 CVCL_1600 Plasma cell myeloma Homo sapiens
U266B1 CVCL_0566 Plasma cell myeloma Homo sapiens
OPM-2 CVCL_1625 Plasma cell myeloma Homo sapiens
KMS-11 CVCL_2989 Plasma cell myeloma Homo sapiens
RPMI-8226 CVCL_0014 Plasma cell myeloma Homo sapiens
KMS-28PE CVCL_2995 Plasma cell myeloma Homo sapiens
                    In-vivo Model The two models employed included an orthotopic murine model (NOD/SCID-gamma mice injected intravenously via tail vein with 5*106 PS-R (bortezomib-resistant U266) stably transfected with a construct encoding luciferase) and an immunocompetent model (C57BL/KaLwR1 mice injected intravenously via tail vein with 5*106 murine MM 5TGM1 cells stably expressing luciferase.
                    Experimental
                    Result(s)		 Flavopiridol enhances ABT-199 sensitivity in unfavourable-risk multiple myeloma cells in vitro and in vivo.
          Irinotecan      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2 phase
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    In-vivo Model Athymic-NCr-nu male mice (8-10 weeks of age) were inoculated subcutaneously in the flank with minced p21-intact HCT116 cells mixed with Matrigel.
                    Experimental
                    Result(s)		 CPT-11 induces cell cycle arrest rather than cell death and that flavopiridol, by activating the caspase cascade, cleaves the inhibitors of apoptosis and sensitizes the cells to undergo cell death.
          Pyrrolo-1,5-benzoxazepine      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 [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
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Acceleration Exit from G2/M transition
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
LAMA-84 CVCL_0388 Chronic myelogenous leukemia Homo sapiens
Ba/F3 CVCL_0161 Healthy Mus musculus
                    Experimental
                    Result(s)		 Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells.
          Tumor necrosis factor alpha      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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Down-regulation Chromosome
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HCT 15 CVCL_0292 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The cytotoxic synergy by the combination treatment involved the activation of caspase-1, caspase-3, and caspase-8 and generated huge chromosomal degradation. TNF-alpha treatment resulted in nuclear factor (NF)-kappa B activation, while flavopiridol inhibited the NF-kappa B-dependent gene transcription.
          4-hydroxy-tamoxifen      Cyclic Mastalgia     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Activity CASP2  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Arrest Cell cycle arrest in G2 phase
                    In-vitro Model MON CVCL_M846 Extrarenal rhabdoid tumor Homo sapiens
G-401 CVCL_0270 Rhabdoid tumor of the kidney Homo sapiens
A-204 CVCL_1058 Embryonal rhabdomyosarcoma Homo sapiens
                    Experimental
                    Result(s)		 Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Death-inducing signaling complex (DISC) formation
Up-regulation Cytochrome c release
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
Evsa-T CVCL_1207 Breast carcinoma Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol sensitizes breast cancer cells to TRAIL-induced apoptosis by facilitating early events in the apoptotic pathway.
          Bortezomib      Mantle 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 Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CRKL  Molecule Info 
Pathway MAP
Up-regulation Expression DIABLO  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation HCK  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JTK8  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT5B  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
Up-regulation Cytochrome c release
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
LAMA-84 CVCL_0388 Chronic myelogenous leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
Raji CVCL_0511 EBV-related Burkitt lymphoma Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
CCRF-CEM CVCL_0207 T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Bortezomib interacts synergistically with flavopiridol to induce mitochondrial dysfunction and apoptosis, blockade of the IkappaB/NF-kappaB pathway and activation of the SAPK/JNK cascade.
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression DIABLO  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
LAMA-84 CVCL_0388 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells.
          Carfilzomib      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 [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M phase
                    In-vitro Model NCI-H295R CVCL_0458 Adrenal cortex carcinoma Homo sapiens
SW13 CVCL_0542 Adrenal cortex carcinoma Homo sapiens
                    In-vivo Model A total of 5*106 NCI-H295R cells with luciferase reporter were injected into each flank of a Nu/Nu mouse (two xenografts per mouse).
                    Experimental
                    Result(s)		 Treatment with flavopiridol and carfilzomib in all three ACC cell lines resulted in a dose-dependent, anti-proliferative effect, and the combination had synergistic activity as well as in three-dimensional tumor spheroids. The combination treatment increased G2M cell-cycle arrest and apoptosis, and decreased XIAP protein expression in ACC cell lines.
          Depsipeptide      Mycosis fungoides     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
                    In-vitro Model NCI-H322 CVCL_1556 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
TE-12 CVCL_1762 Esophageal squamous cell carcinoma Homo sapiens
TE-13 CVCL_4463 Esophageal squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The depsipeptide plus flavopiridol combination exhibits powerful and selective cytocidal activity against cancer but not normal cells. Apoptosis induced by this combination is mediated by the mitochondria-dependent death pathway.
          Vorinostat      Mycosis fungoides     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		 Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression MAD2L1  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
                    In-vitro Model CHLA-15 CVCL_6594 Neuroblastoma Homo sapiens
CHLA-20 CVCL_6602 Neuroblastoma Homo sapiens
SK-N-BE(1) CVCL_9898 Neuroblastoma Homo sapiens
SK-N-RA CVCL_AQ53 Neuroblastoma Homo sapiens
LA-N-6 CVCL_1363 Neuroblastoma Homo sapiens
CHLA-136 CVCL_6590 Neuroblastoma Homo sapiens
CHLA-79 CVCL_6608 Neuroblastoma Homo sapiens
CHLA-119 CVCL_A055 Neuroblastoma Homo sapiens
CHLA-90 CVCL_6610 Neuroblastoma Homo sapiens
CHLA-172 CVCL_A056 Neuroblastoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of vorinostat and flavopiridol is selectively cytotoxic to multidrug-resistant neuroblastoma cell lines with mutant TP53. The combination caused reduction in the expression of G(2)/M proteins (cyclin B1, Mad2, MPM2) in 2 cell lines with mt TP53 but not in those with wt TP53.
          Doxorubicin      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 [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression NDRG1  Molecule Info 
Pathway MAP
                    In-vivo Model Subcutaneous injections of 2.5*105 viable MH134 cells suspended in 0.1 mL of media were performed in the right flanks of five-week-old male C3H/He mice, creating a bleb.
                    Experimental
                    Result(s)		 Combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 E2F1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RRM2  Molecule Info 
Pathway MAP
                    In-vitro Model MKN74 CVCL_2791 Gastric tubular adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
Capan-2 CVCL_0026 Pancreatic ductal adenocarcinoma Homo sapiens
SK-GT-5 CVCL_8114 Gastric adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit (RR-M2).
          Anti-CD25 monoclonal antibody      Acute lymphoblastic 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 [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model FCCH1043 CVCL_M518 Adult T acute lymphoblastic leukemia Homo sapiens
MT-2 CVCL_2631 Healthy Homo sapiens
HuT 102 CVCL_3526 Mycosis fungoides and Sezary syndrome Homo sapiens
                    In-vivo Model The xenograft model was established by intraperitoneal injection of 1.5*107 MET-1 cells into SCID/NOD mice.
                    Experimental
                    Result(s)		 Combination of the flavopiridol and anti-CD25 monoclonal antibody dramatically enhanced the antitumor effect.
          Cisplatin      Bladder 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
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Administration of flavopiridol for 24 h followed 3 days later by exposure to 5-fluorouracil resulted in a highly synergistic interaction.
          Rev-caspase-3      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 [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model OVCAR-3 CVCL_0465 Ovarian serous adenocarcinoma Homo sapiens
                    In-vivo Model 1*107 OVCAR3 cells in 0.2 ml PBS were inoculated subcutaneously into the dorsal flank of female mice (4 to 6 weeks old and weighing 16 to 20 g).
                    Experimental
                    Result(s)		 The sequential combination of rev-caspase-3 and flavopiridol result in significant synergistic cell killing effects, significant tumor growth suppression and extended survival of mice bearing OVCAR3 cells.
          Mitomycin C      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
                    In-vitro Model MKN74 CVCL_2791 Gastric tubular adenocarcinoma Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol potentiates the cytotoxic effect of the chemotherapeutic agent MMC by promoting drug-induced apoptosis in tumor cells.
Target and Pathway
Target(s) Cyclin-dependent kinase (CDK)  Molecule Info  [20]
Cyclin-dependent kinase 9 (CDK9)  Molecule Info  [21]
Myophosphorylase (PYGM)  Molecule Info  [20]
KEGG Pathway Transcriptional misregulation in cancer Click to Show/Hide
NetPath Pathway EGFR1 Signaling Pathway Click to Show/Hide
Reactome SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription Click to Show/Hide
WikiPathways Cardiac Hypertrophic Response Click to Show/Hide
2 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
3 Host Interactions of HIV factors
4 HIV Life Cycle
5 IL-9 Signaling Pathway
6 RNA Polymerase II Transcription
7 MicroRNAs in cardiomyocyte hypertrophy
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5680).
Reference 2 Epidermal growth factor receptor expression is a candidate target of the synergistic combination of trastuzumab and flavopiridol in breast cancer. Cancer Res. 2003 Jul 1;63(13):3626-31.
Reference 3 Flavopiridol enhances ABT-199 sensitivity in unfavourable-risk multiple myeloma cells in vitro and in vivo. Br J Cancer. 2018 Feb 6;118(3):388-397.
Reference 4 Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. Clin Cancer Res. 2001 Dec;7(12):4209-19.
Reference 5 Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells including those resistant to imatinib treatment. Biochem Pharmacol. 2010 Jul 1;80(1):31-8.
Reference 6 Rapid induction of apoptosis by combination of flavopiridol and tumor necrosis factor (TNF)-alpha or TNF-related apoptosis-inducing ligand in human cancer cell lines. Cancer Res. 2003 Feb 1;63(3):621-6.
Reference 7 Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen. BMC Cancer. 2010 Nov 19;10:634.
Reference 8 Flavopiridol induces cellular FLICE-inhibitory protein degradation by the proteasome and promotes TRAIL-induced early signaling and apoptosis in breast tumor cells. Cancer Res. 2006 Sep 1;66(17):8858-69.
Reference 9 Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood. 2004 Jul 15;104(2):509-18.
Reference 10 Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells. Clin Cancer Res. 2002 Sep;8(9):2976-84.
Reference 11 Synergistic combination of flavopiridol and carfilzomib targets commonly dysregulated pathways in adrenocortical carcinoma and has biomarkers of response. Oncotarget. 2018 Aug 31;9(68):33030-33042.
Reference 12 Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. J Thorac Cardiovasc Surg. 2003 May;125(5):1132-42.
Reference 13 Combination of vorinostat and flavopiridol is selectively cytotoxic to multidrug-resistant neuroblastoma cell lines with mutant TP53. Mol Cancer Ther. 2010 Dec;9(12):3289-301.
Reference 14 Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model. J Cancer Res Clin Oncol. 2015 Nov;141(11):2037-45.
Reference 15 Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit. Clin Cancer Res. 2001 Aug;7(8):2527-36.
Reference 16 Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody. Blood. 2005 Feb 1;105(3):1231-6.
Reference 17 Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: the importance of sequence of administration. Cancer Res. 1997 Aug 15;57(16):3375-80.
Reference 18 Sequential combination therapy with flavopiridol and autocatalytic caspase-3 driven by amplified hTERT promoter synergistically suppresses human ovarian carcinoma growth in vitro and in mice. J Ovarian Res. 2014 Dec 21;7:121.
Reference 19 Potentiation of apoptosis by flavopiridol in mitomycin-C-treated gastric and breast cancer cells. Clin Cancer Res. 1997 Sep;3(9):1467-72.
Reference 20 Pharma & Vaccines. Product Development Pipeline. April 29 2009.
Reference 21 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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