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

General Information of Drug (ID: DM0FROP)

• Drug Name: Nafoxidine Drug Info
• Synonyms: Nafoxidine; 1845-11-0; Nafoxidine [INN]; Nafoxidinum [INN-Latin]; Nafoxidina [INN-Spanish]; UNII-4RIY10WM82; U-11000A; BRN 1440873; CHEMBL28211; 4RIY10WM82; CHEBI:34881; NSC 70735; C29H31NO2; JEYWNNAZDLFBFF-UHFFFAOYSA-N; 1-(2-(p-(3,4-Dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy)ethyl)pyrrolidine; Pyrrolidine, 1-(2-(4-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl)phenoxy)ethyl)-; 1-[2-[4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine; Pyrrolidine, 1-(2-(p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl

Indication

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

• Cross-matching ID:
  PubChem CID: 4416
  ChEBI ID: CHEBI:34881
  CAS Number: CAS 1845-11-0
  TTD Drug ID: DM0FROP
  VARIDT Drug ID: DR01340

Molecule-Related Drug Atlas

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated Estrogens	DMLT0E1	Dyspareunia	GA12	Approved	[4]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[5]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[6]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[7]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[8]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[9]
AUS-131	DMUXO3Z	Hot flushes	GA30	Phase 2	[10]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[11]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[12]
VG-101	DMAN21O	Menopause symptom	GA30.0	Phase 1/2	[13]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[15]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[5]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[5]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[5]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[16]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[17]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[18]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[19]

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	[20]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[23]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[22]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[22]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[3]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[25]

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	[2]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[2]

Drug Transporter (DTP)

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

References

• [1] 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: 4263).
• [2] Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthal... J Med Chem. 1998 Jul 30;41(16):2928-31.
• [3] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [4] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [7] 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.
• [8] 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.
• [9] Company report (Axcentua)
• [10] 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.
• [11] 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.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [13] Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence. 2011; 5: 533-536.
• [14] 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.
• [15] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [16] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [17] 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).
• [18] Clinical pipeline report, company report or official report of Shionogi (2011).
• [19] 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.
• [20] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [21] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [22] 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.
• [23] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [24] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [25] 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.