Details of the Drug

General Information of Drug (ID: DMKSUOI)

Drug 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
Indication
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 2 [1]
Chronic lymphocytic leukaemia 2A82.0 Discontinued in Phase 3 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 401.8
Logarithm of the Partition Coefficient (xlogp) 3.3
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C21H20ClNO5
IUPAC Name
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one
Canonical SMILES
CN1CC[C@@H]([C@@H](C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O
InChI
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
Cross-matching ID
PubChem CID
5287969
ChEBI ID
CHEBI:47344
CAS Number
146426-40-6
DrugBank ID
DB03496
TTD ID
D0LF1U
VARIDT ID
DR00235
INTEDE ID
DR0079
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase (CDK) TTMBO1Z NOUNIPROTAC Inhibitor [3]
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [4]
Myophosphorylase (PYGM) TT31JXP PYGM_HUMAN Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)
Main DME 		DEYGVN4 UD11_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [9]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Gene/Protein Processing [10]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [10]
BAG family molecular chaperone regulator 1 (BAG1) OTRQNIA4 BAG1_HUMAN Gene/Protein Processing [9]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [10]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Protein Interaction/Cellular Processes [11]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Gene/Protein Processing [12]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [13]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Protein Interaction/Cellular Processes [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute myeloid leukaemia
ICD Disease Classification 2A60
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 9 (CDK9) DTT CDK9 4.38E-01 -0.04 -0.1
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 2.80E-34 1.44E-01 9.71E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 2.33E-02 1.75E-02 8.91E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 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).
3 Pharma & Vaccines. Product Development Pipeline. April 29 2009.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR-associated ATP-binding cassette transporter ABCG2. Mol Cancer Ther. 2012 Sep;11(9):2033-44.
6 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
7 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
8 Flavopiridol induces apoptosis in glioma cell lines independent of retinoblastoma and p53 tumor suppressor pathway alterations by a caspase-independent pathway. Mol Cancer Ther. 2003 Feb;2(2):139-50.
9 Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood. 2005 Oct 1;106(7):2513-9. doi: 10.1182/blood-2005-04-1678. Epub 2005 Jun 21.
10 Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis. Cancer Res. 2003 Jan 1;63(1):93-9.
11 The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway. Cell Death Differ. 2001 Jul;8(7):715-24. doi: 10.1038/sj.cdd.4400868.
12 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. doi: 10.1158/0008-5472.CAN-06-0808.
13 Flavopiridol induces apoptosis and caspase-3 activation of a newly characterized Burkitt's lymphoma cell line containing mutant p53 genes. Blood Cells Mol Dis. 2001 May-Jun;27(3):610-24. doi: 10.1006/bcmd.2001.0428.
14 Bcl-2 independence of flavopiridol-induced apoptosis. Mitochondrial depolarization in the absence of cytochrome c release. J Biol Chem. 2000 Oct 13;275(41):32089-97. doi: 10.1074/jbc.M005267200.