Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM40TBU)

• Drug Name: Coumestrol Drug Info
• Synonyms: COUMESTROL; 479-13-0; Cumoestrol; Cumoesterol; Cumostrol; Coumesterol; 3,9-Dihydroxy-6H-[1]benzofuro[3,2-c]chromen-6-one; 7,12-Dihydroxycoumestan; 3,9-Dihydroxycoumestan; UNII-V7NW98OB34; NSC 22842; CCRIS 7311; NSC22842; 6H-Benzofuro[3,2-c][1]benzopyran-6-one, 3,9-dihydroxy-; EINECS 207-525-6; BRN 0266702; CHEMBL30707; MLS000738006; V7NW98OB34; CHEBI:3908; ZZIALNLLNHEQPJ-UHFFFAOYSA-N; 3,9-Dihydroxy-6H-benzofuro(3,2-c)(1)benzopyran-6-one; 6H-Benzofuro(3,2-c)(1)benzopyran-6-one, 3,9-dihydroxy-

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5281707
  ChEBI ID: CHEBI:3908
  CAS Number: CAS 479-13-0
  TTD Drug ID: DM40TBU
  VARIDT Drug ID: DR00932

Molecule-Related Drug Atlas

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[4]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[5]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[8]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[9]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[8]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated estrogens	DMLT0E1	Menopause symptom	GA30.0	Approved	[12]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[13]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[14]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[15]
Premarin/Pravachol	DMLSOB7	Hyperlipidaemia	5C80	Phase 3	[16]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[17]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[18]
AUS-131	DMZMSQJ	Hot flushes	GA30	Phase 2	[19]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[20]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[21]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[23]
Estrone	DM5T6US	Menopausal and postmenopausal disorder	GA30	Approved	[23]
Estradiol valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[13]
Estradiol acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[13]
Estradiol cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[13]
Ethinyl estradiol	DMODJ40	Female hypogonadism	GA30.6	Approved	[24]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[25]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[26]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Inhibitor	[1]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[2]

References

• [1] Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative ... J Med Chem. 2005 May 19;48(10):3463-6.
• [2] Effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of phytoestrogens. Mol Pharmacol. 2007 Oct;72(4):967-75.
• [3] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [4] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [5] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [6] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [7] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [8] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [9] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [10] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [11] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [12] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [14] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [15] Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15133-6.
• [16] Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003 Jul;2(7):517-26.
• [17] MF101, a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes: a phase II clinical trial. Menopause. 2009 May-Jun;16(3):458-65.
• [18] Company report (Axcentua)
• [19] S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9.
• [20] Erb-041, an estrogen receptor-beta agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila). 2014 Feb;7(2):186-98.
• [21] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [22] Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
• [23] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [24] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [25] 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. (Target id: 620).
• [26] Clinical pipeline report, company report or official report of Shionogi (2011).
• [27] Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.