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

General Information of Drug (ID: DMXLZAT)

• Drug Name: 4-Ethynyl-2-(4-hydroxy-phenyl)-quinolin-6-ol Drug Info
• Synonyms: 4-ethynyl-2-(4-hydroxyphenyl)quinolin-6-ol

Indication

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

• Cross-matching ID:
  PubChem CID: 135524856
  TTD Drug ID: DMXLZAT

Molecule-Related Drug Atlas

Drug(s) Targeting Estrogen-related receptor-alpha (ESRRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rimexolone	DMTAREC	Arthritis	FA20	Approved	[3]
Pregnenolone	DM6VFO1	Schizophrenia	6A20	Phase 4	[4]
D-5519	DM9FAJM	Asthma	CA23	Phase 3	[5]
Dexamethasone palmitate	DMCMT4V	Choroidal neovascularization	9B76	Phase 1/2	[6]
RPR-106541	DMRGC5B	Asthma	CA23	Discontinued in Phase 2	[7]
Rofleponide	DM6OSPQ	Allergic rhinitis	CA08.0	Discontinued in Phase 2	[8]
AD-121	DMB8XJM	Rheumatoid arthritis	FA20	Discontinued in Phase 1/2	[3]
GW-250495	DMWJZAP	Asthma	CA23	Discontinued in Phase 1	[3]
PLD-177	DMPHUBO	Allergic rhinitis	CA08.0	Terminated	[3]
Steroid hormone conjugates	DMOJM08	Cachexia	MG20	Terminated	[9]

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated Estrogens	DMLT0E1	Dyspareunia	GA12	Approved	[10]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[11]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[12]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[13]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[14]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[15]
AUS-131	DMUXO3Z	Hot flushes	GA30	Phase 2	[16]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[17]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[18]
VG-101	DMAN21O	Menopause symptom	GA30.0	Phase 1/2	[19]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[21]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[21]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[11]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[11]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[11]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[22]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[23]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[24]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	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	[1]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[1]
Estrogen-related receptor-alpha (ESRRA)	TTPNQAC	ERR1_HUMAN	Inhibitor	[2]

References

• [1] ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenylquinoline derivatives. Bioorg Med Chem Lett. 2005 Oct 15;15(20):4520-5.
• [2] ERbeta ligands. Part 6: 6H-Chromeno[4,3-b]quinolines as a new series of estrogen receptor beta-selective ligands. Bioorg Med Chem Lett. 2007 Jul 15;17(14):4053-6.
• [3] 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: 622).
• [4] Suppression of adrenal function by low-dose prednisone: assessment with 24-hour urinary steroid hormone profiles--a review of five cases. Altern Med Rev. 2006 Mar;11(1):40-6.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007199)
• [6] Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet. 2002 Jul 20;360(9328):211-8.
• [7] Use of the steroid derivative RPR 106541 in combination with site-directed mutagenesis for enhanced cytochrome P-450 3A4 structure/function analysis. J Pharmacol Exp Ther. 1999 Aug;290(2):594-602.
• [8] Direct activation of GABAA receptors by loreclezole, an anticonvulsant drug with selectivity for the beta-subunit. Neuropharmacology. 1996;35(12):1753-60.
• [9] The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf). 1998 Oct;49(4):421-32.
• [10] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [13] 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.
• [14] 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.
• [15] Company report (Axcentua)
• [16] 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.
• [17] 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.
• [18] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [19] Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence. 2011; 5: 533-536.
• [20] 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.
• [21] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [22] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [23] 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).
• [24] Clinical pipeline report, company report or official report of Shionogi (2011).
• [25] 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.