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Identification
NameGenistein
Accession NumberDB01645  (EXPT01582)
TypeSmall Molecule
GroupsInvestigational
Description

An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-II (DNA topoisomerases, type II) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines.

Additionally, genistein has antihelmintic activity. It has been determined to be the active ingredient in Felmingia vestita, which is a plant traditionally used against worms. It has also been demonstrated to be effective against intestinal parasites such as the common liver fluke, pork trematode and poultry cestode. [Wikipedia]

Further, genistein is a phytoestrogen which has selective estrogen receptor modulator properties. It has been investigated in clinical trials as an alternative to classical hormone therapy to help prevent cardiovascular disease in postmenopausal women. 1

Genistein can be found in food sources such as tofu, fava beans, soybeans, kudzu, and lupin. It is also present in certain cell cultures and medicinal plants. [Wikipedia]

Structure
Thumb
Synonyms
4',5, 7-Trihydroxyisoflavone
5,7,4'-Trihydroxyisoflavone
Genisteol
Genisterin
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
PrunetolNot Available
SophoricolNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIDH2M523P0H
CAS number446-72-0
WeightAverage: 270.2369
Monoisotopic: 270.05282343
Chemical FormulaC15H10O5
InChI KeyInChIKey=TZBJGXHYKVUXJN-UHFFFAOYSA-N
InChI
InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H
IUPAC Name
5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
SMILES
OC1=CC=C(C=C1)C1=COC2=C(C(O)=CC(O)=C2)C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as isoflavones. These are polycyclic compounds containing a 2-isoflavene skeleton which bears a ketone group at the C4 carbon atom.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassIsoflavonoids
Sub ClassIsoflav-2-enes
Direct ParentIsoflavones
Alternative Parents
Substituents
  • Hydroxyisoflavonoid
  • Isoflavone
  • Chromone
  • 1-benzopyran
  • Benzopyran
  • Resorcinol
  • Pyranone
  • Phenol
  • Benzenoid
  • Pyran
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous acid
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationCurrently Genistein is being studied in clinical trials as a treatment for prostate cancer.
PharmacodynamicsNot Available
Mechanism of actionGenistein may inhibit cancer cell growth by blocking enzymes required for cell growth. Genistein may decrease cardiovascular risk in postmenopausal women by interacting with the nuclear estrogen receptors to alter the transcription of cell specific genes. In randomized clinical trials, genistein was seen to increase the ratio of nitric oxide to endothelin and improved flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. [1] In addition, genistein may have beneficial effects on glucose metabolism by inhibiting islet tyrosine kinase activity as well as insulin release dependent on glucose and sulfonylurea. [1]
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Genistein
3'-hydroxygenisteinDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
  • Helminthic Microorganisms
  • Parasitic nematodes and other roundworms
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9877
Blood Brain Barrier+0.6785
Caco-2 permeable+0.7002
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.9288
P-glycoprotein inhibitor IINon-inhibitor0.7828
Renal organic cation transporterNon-inhibitor0.9075
CYP450 2C9 substrateNon-substrate0.7672
CYP450 2D6 substrateNon-substrate0.9105
CYP450 3A4 substrateNon-substrate0.6821
CYP450 1A2 substrateInhibitor0.9254
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorInhibitor0.8881
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8009
Ames testNon AMES toxic0.9638
CarcinogenicityNon-carcinogens0.9276
BiodegradationNot ready biodegradable0.8572
Rat acute toxicity3.2988 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9569
hERG inhibition (predictor II)Non-inhibitor0.8917
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 Properties
PropertyValueSource
melting point301.5 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.123 mg/mLALOGPS
logP3.04ALOGPS
logP3.08ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)6.61ChemAxon
pKa (Strongest Basic)-5.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.99 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity71.68 m3·mol-1ChemAxon
Polarizability26.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-1da7z00000-1dd6fcaf99898bd949dfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-zo10000000-04b546320e268d817276View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-nz70000000-7e265d1b4640f882195aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-7zo0000000-7843ec8ae23314f88147View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-2bz0000000-52ec910b223a3688fbc0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-14z0000000-4045f471e10774927fb0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-01z0000000-b593f863241cb83cbaa8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-APPI-QQ (API2000) , Positivesplash10-05z3000000-0cd8d123608bd54f7214View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 5V, Positivesplash10-00z0000000-9ce354d07dc39313259bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-3z60000000-5eb75a138568fa4ac897View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-9z80000000-a32f6ae97952bb96de05View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-29z0000000-4592d557e739a114cbfaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF (LCMS-IT-TOF) , Positivesplash10-00z0000000-14ae481944ad1a1f7ca0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF (LCMS-IT-TOF) , Negativesplash10-12z10c0000-a3400b0a77da6983528fView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
Synthesis Reference

J. Mark Weber, Andreas Constantinou, Paul E. Hessler, “Process of preparing genistein.” U.S. Patent US5554519, issued June, 1994.

US5554519
General References

1. Crisafulli, Alessandra, et al. “Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women.” Menopause 12.2 (2005): 186-192.

2. Toner, E., et al. “Physiological and morphological effects of genistein against the liver fluke, Fasciola hepatica.” Parasitology 135.10 (2008): 1189.

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

Targets

1. Estrogen receptor beta

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Estrogen receptor beta Q92731 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. DNA topoisomerase 2-alpha

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
DNA topoisomerase 2-alpha P11388 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. Protein-tyrosine kinase 2-beta

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Protein-tyrosine kinase 2-beta Q14289 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

4. Nuclear receptor coactivator 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nuclear receptor coactivator 1 Q15788 Details

References:

  1. 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

5. Estrogen receptor

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Estrogen receptor P03372 Details

References:

  1. 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

6. Nuclear receptor coactivator 2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nuclear receptor coactivator 2 Q15596 Details

References:

  1. 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

Enzymes

1. Cytochrome P450 1A2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Hu M, Krausz K, Chen J, Ge X, Li J, Gelboin HL, Gonzalez FJ: Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab Dispos. 2003 Jul;31(7):924-31. Pubmed

Carriers

1. Transthyretin

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Transthyretin P02766 Details

References:

  1. 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

Transporters

1. Multidrug resistance protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Castro AF, Altenberg GA: Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein. Biochem Pharmacol. 1997 Jan 10;53(1):89-93. Pubmed
  2. Versantvoort CH, Rhodes T, Twentyman PR: Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds. Br J Cancer. 1996 Dec;74(12):1949-54. Pubmed
  3. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed

2. Multidrug resistance-associated protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Pec MK, Aguirre A, Fernandez JJ, Souto ML, Dorta JF, Villar J: Dehydrothyrsiferol does not modulate multidrug resistance-associated protein 1 resistance: a functional screening system for MRP1 substrates. Int J Mol Med. 2002 Nov;10(5):605-8. Pubmed
  2. Nguyen H, Zhang S, Morris ME: Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. J Pharm Sci. 2003 Feb;92(2):250-7. Pubmed
  3. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. Pubmed
  4. Versantvoort CH, Rhodes T, Twentyman PR: Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds. Br J Cancer. 1996 Dec;74(12):1949-54. Pubmed

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

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

References:

  1. Imai Y, Tsukahara S, Asada S, Sugimoto Y: Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res. 2004 Jun 15;64(12):4346-52. Pubmed
  2. Zhang S, Yang X, Morris ME: Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol. 2004 May;65(5):1208-16. Pubmed
  3. Perez M, Real R, Mendoza G, Merino G, Prieto JG, Alvarez AI: Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones. J Vet Pharmacol Ther. 2009 Oct;32(5):498-502. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:15