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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
SynonymLanguageCode
AlvocidibNot AvailableINN
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Flavopiridol hydrochloride
Thumb
  • InChI Key: LGMSNQNWOCSPIK-LWHGMNCYSA-N
  • Monoisotopic Mass: 437.079678201
  • Average Mass: 438.301
DBSALT000800
Categories
CAS number131740-09-5
WeightAverage: 401.84
Monoisotopic: 401.103000462
Chemical FormulaC21H20ClNO5
InChI KeyBIIVYFLTOXDAOV-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]([C@H](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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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 substrateNon-inhibitor0.8621
CYP450 2D6 substrateNon-inhibitor0.7374
CYP450 2C19 substrateNon-inhibitor0.7358
CYP450 3A4 substrateNon-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
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 ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Glycogen phosphorylase, muscle form

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Glycogen phosphorylase, muscle form P11217 Details

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
  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
  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

2. Cyclin-dependent kinase 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 7 P50613 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Cyclin-dependent kinase 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 5 Q00535 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Cyclin-dependent kinase 9

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 9 P50750 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

5. Cyclin-dependent kinase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 1 P06493 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

6. Cyclin-dependent kinase 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 6 Q00534 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

7. Epidermal growth factor receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Epidermal growth factor receptor P00533 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

8. Cyclin-dependent kinase 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 4 P11802 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

9. Cyclin-dependent kinase 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cyclin-dependent kinase 8 P49336 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

10. Cyclin-dependent kinase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cyclin-dependent kinase 2 P24941 Details

References:

  1. Zvelebil MJ: Flavopiridol (Hoechst AG). IDrugs. 1998 Jun;1(2):241-6. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Transporters

1. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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
  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
  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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:21