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Identification
NameFlavopiridol
Accession NumberDB03496  (EXPT00998)
TypeSmall Molecule
GroupsExperimental, Investigational
Description

Flavopiridol is a synthetic flavonoid based on an extract from an Indian plant for the potential treatment of cancer. It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.

Structure
Thumb
Synonyms
Alvocidib
Alvocidib freebase
External Identifiers
  • HMR-1275
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Flavopiridol hydrochloride
131740-09-5
Thumb
  • InChI Key: LGMSNQNWOCSPIK-LWHGMNCYSA-N
  • Monoisotopic Mass: 437.079678201
  • Average Mass: 438.301
DBSALT000800
Categories
UNII45AD6X575G
CAS number146426-40-6
WeightAverage: 401.84
Monoisotopic: 401.103000462
Chemical FormulaC21H20ClNO5
InChI KeyInChIKey=BIIVYFLTOXDAOV-YVEFUNNKSA-N
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
IUPAC Name
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-chromen-4-one
SMILES
CN1CC[C@@H]([[email protected]](O)C1)C1=C(O)C=C(O)C2=C1OC(=CC2=O)C1=CC=CC=C1Cl
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as flavones. These are flavonoids with a structure based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassFlavonoids
Sub ClassFlavones
Direct ParentFlavones
Alternative Parents
Substituents
  • Hydroxyflavonoid
  • Flavone
  • 7-hydroxyflavonoid
  • 5-hydroxyflavonoid
  • Phenylpiperidine
  • Chromone
  • 1-benzopyran
  • Benzopyran
  • Resorcinol
  • Aralkylamine
  • Pyranone
  • Halobenzene
  • Chlorobenzene
  • Benzenoid
  • Pyran
  • Piperidine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Vinylogous acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in esophageal cancer, leukemia (lymphoid), lung cancer, liver cancer, and lymphoma (unspecified).
PharmacodynamicsNot Available
Mechanism of actionInhibits cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier-0.557
Caco-2 permeable+0.6029
P-glycoprotein substrateSubstrate0.9095
P-glycoprotein inhibitor INon-inhibitor0.8213
P-glycoprotein inhibitor IINon-inhibitor0.7929
Renal organic cation transporterNon-inhibitor0.6429
CYP450 2C9 substrateNon-substrate0.7975
CYP450 2D6 substrateNon-substrate0.6651
CYP450 3A4 substrateSubstrate0.6517
CYP450 1A2 substrateNon-inhibitor0.6845
CYP450 2C9 inhibitorNon-inhibitor0.8621
CYP450 2D6 inhibitorNon-inhibitor0.7374
CYP450 2C19 inhibitorNon-inhibitor0.7358
CYP450 3A4 inhibitorNon-inhibitor0.9008
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8937
Ames testNon AMES toxic0.7686
CarcinogenicityNon-carcinogens0.9375
BiodegradationNot ready biodegradable0.9923
Rat acute toxicity2.7659 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5312
hERG inhibition (predictor II)Non-inhibitor0.715
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.094 mg/mLALOGPS
logP2.81ALOGPS
logP2.48ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)6.71ChemAxon
pKa (Strongest Basic)7.36ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area90.23 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity107.74 m3·mol-1ChemAxon
Polarizability40.85 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Kyoung Soon Kim, “Process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs.” U.S. Patent US5908934, issued March, 1998.

US5908934
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Pyridoxal phosphate binding
Specific Function:
Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
Gene Name:
PYGM
Uniprot ID:
P11217
Molecular Weight:
97091.265 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transcription coactivator activity
Specific Function:
Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cycl...
Gene Name:
CDK7
Uniprot ID:
P50613
Molecular Weight:
39038.005 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tau-protein kinase activity
Specific Function:
Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK1...
Gene Name:
CDK5
Uniprot ID:
Q00535
Molecular Weight:
33304.125 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transcription regulatory region dna binding
Specific Function:
Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This com...
Gene Name:
CDK9
Uniprot ID:
P50750
Molecular Weight:
42777.155 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function:
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, C...
Gene Name:
CDK1
Uniprot ID:
P06493
Molecular Weight:
34095.14 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Cyclin-dependent protein serine/threonine kinase activity
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation...
Gene Name:
CDK6
Uniprot ID:
Q00534
Molecular Weight:
36938.025 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on ke...
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function:
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progres...
Gene Name:
CDK4
Uniprot ID:
P11802
Molecular Weight:
33729.55 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ubiquitin protein ligase activity
Specific Function:
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold fo...
Gene Name:
CDK8
Uniprot ID:
P49336
Molecular Weight:
53283.335 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synt...
Gene Name:
CDK2
Uniprot ID:
P24941
Molecular Weight:
33929.215 Da
References
  1. Zvelebil MJ: Flavopiridol Hoechst AG. IDrugs. 1998 Jun;1(2):241-6. [PubMed:18465538 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Nakanishi T, Karp JE, Tan M, Doyle LA, Peters T, Yang W, Wei D, Ross DD: Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res. 2003 Aug 15;9(9):3320-8. [PubMed:12960118 ]
  2. Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. [PubMed:14645676 ]
  3. Shi Z, Parmar S, Peng XX, Shen T, Robey RW, Bates SE, Fu LW, Shao Y, Chen YM, Zang F, Chen ZS: The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance. Oncol Rep. 2009 Feb;21(2):483-9. [PubMed:19148526 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23