Details of the Drug

General Information of Drug (ID: DM0JETC)

• Drug Name: Genistein
• Synonyms: Bonistein; GEN; Genestein; Genisteol; Genisterin; Prunetol; Sophoricol; Differenol A; G 6649; G10000; IN1327; NPI 031L; STO514; TNP00151; GENISTEIN (ENDOCRINE DISRUPTER); Lactoferrin-genistein; PTI G4660 (Genistein); PTI-G4660; SIPI 807-1; C.I. 75610; SIPI-9764-I; ENDOCRINE DISRUPTOR (GENISTEIN) (SEE ALSO GENISTEIN (446-72-0)); 4 inverted exclamation marka,5,7-Trihydroxyisoflavone; ,5,7-Trihydroxyisoflavone; 4',5, 7-Trihydroxyisoflavone; 4',5,7-Trihydroxy isoflavone; 4',5,7-Trihydroxyisoflavone; 4,5,7-Trihydroxyiso-flavone; 4,6,7-Trihydroxyisoflavone; 5,7,4'-Trihydroxyisoflavone; 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4-benzopyrone; 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one; 5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one

Indication

Disease Entry	ICD 11	Status	REF
Menopause symptom	GA30.0	Phase 2/3	[1]
Prostate cancer	2C82.0	Phase 2	[2]

• Affected Organisms: Humans and other mammalsHelminthic MicroorganismsParasitic nematodes and other roundworms
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 270.24
  Logarithm of the Partition Coefficient (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C15H10O5
  IUPAC Name: 5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one
  Canonical SMILES: C1=CC(=CC=C1C2=COC3=CC(=CC(=C3C2=O)O)O)O
  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
  InChIKey: TZBJGXHYKVUXJN-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5280961
  ChEBI ID: CHEBI:28088
  CAS Number: 446-72-0
  UNII: DH2M523P0H
  DrugBank ID: DB01645
  TTD ID: D0L4FS
  VARIDT ID: DR00641
  INTEDE ID: DR0768
• 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
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Modulator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[5]
Sulfotransferase 2A1 (SULT2A1)	DE0P6LK	ST2A1_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
(3R)-3-hydroxyacyl-CoA dehydrogenase (HSD17B8)	OTX1DWEF	DHB8_HUMAN	Gene/Protein Processing	[7]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[8]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)	OT5I4Y9K	PLCB_HUMAN	Gene/Protein Processing	[9]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1)	OT9HYT7A	PLCB1_HUMAN	Gene/Protein Processing	[10]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[9]
14-3-3 protein epsilon	OT3WQXNA	1433E_HUMAN	Gene/Protein Processing	[11]
17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14)	OT0ETO72	DHB14_HUMAN	Gene/Protein Processing	[10]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Gene/Protein Processing	[12]
182 kDa tankyrase-1-binding protein (TNKS1BP1)	OTBIZECQ	TB182_HUMAN	Gene/Protein Processing	[7]
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (BCKDHA)	OT0LHOZB	ODBA_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Menopause symptom
• ICD Disease Classification: GA30.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Estrogen receptor beta (ESR2)	DTT	ESR2	1.12E-20	-0.22	-0.7
Breast cancer resistance protein (ABCG2)	DTP	BCRP	1.46E-65	-1.41E+00	-1.41E+00
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	4.34E-02	-5.62E-03	-1.44E-02
Sulfotransferase 2A1 (SULT2A1)	DME	SULT2A1	8.40E-01	5.46E-03	3.67E-02

References

• [1] ClinicalTrials.gov (NCT00355953) Vascular and Skeletal Protective Effects of Genistein in Postmenopausal Women. U.S. National Institutes of Health.
• [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: 2826).
• [3] Company report (Axcentua)
• [4] Differential selectivity of efflux transporter inhibitors in Caco-2 and MDCK-MDR1 monolayers: a strategy to assess the interaction of a new chemical entity with P-gp, BCRP, and MRP2. J Pharm Sci. 2012 May;101(5):1888-97.
• [5] Differential mechanisms for the inhibition of human cytochrome P450 1A2 by apigenin and genistein. J Biochem Mol Toxicol. 2010 Jul-Aug;24(4):230-4.
• [6] Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab Pharmacokinet. 2002;17(3):221-8.
• [7] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [8] Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: role of the direct inhibition of CYP24 enzyme activity. Mol Cell Endocrinol. 2005 Sep 28;241(1-2):49-61.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [11] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [12] Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.