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

General Information of Drug (ID: DM9JPUD)

• Drug Name: Droloxifene Drug Info
• Synonyms: E-droloxifene; FK-435; K-060; K-060E; RP-60850; K-21.060E; 3-hydroxytamoxifen

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 3033767
  ChEBI ID: CHEMBL34731
  CAS Number: CAS 82413-20-5
  TTD Drug ID: DM9JPUD
  VARIDT Drug ID: DR01424

Molecule-Related Drug Atlas

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[5]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[6]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[6]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[7]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[7]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[7]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[8]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[9]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[10]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[11]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[3]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[13]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]

Drug(s) Affected By Sex hormone-binding globulin (SHBG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[18]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[19]
Fructose	DM43AN2	Vomiting	MD90	Approved	[20]
Oxcarbazepine	DM5PU6O	Epilepsy	8A60-8A68	Approved	[21]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[4]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[22]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[23]
Dienestrol	DMBSXI0	Atrophic vaginitis	GA30.2	Approved	[4]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[4]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000847)
• [2] Droloxifene, a new antiestrogen: its role in metastatic breast cancer. Breast Cancer Res Treat. 1994;31(1):83-94.
• [3] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [4] Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and -fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27.
• [5] 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.
• [6] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [9] 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).
• [10] Clinical pipeline report, company report or official report of Shionogi (2011).
• [11] 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.
• [12] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [13] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [14] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [15] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [16] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [17] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [18] Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties. Contraception. 2003 Feb;67(2):93-9. doi: 10.1016/s0010-7824(02)00473-0.
• [19] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [20] Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest. 2007 Dec;117(12):3979-87. doi: 10.1172/JCI32249.
• [21] Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology. 2001 Jan 9;56(1):31-6. doi: 10.1212/wnl.56.1.31.
• [22] Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes. J Endocrinol. 2011 Aug;210(2):219-29. doi: 10.1530/JOE-10-0497. Epub 2011 Jun 1.
• [23] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.