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

General Information of Drug (ID: DM2I8NT)

• Drug Name: Avosentan Drug Info
• Synonyms: SPP 301; SPP301; Ro 67-0565; N-[6-methoxy-5-(2-methoxyphenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-5-methyl-pyridine-2-sulfonamide; 5-methylpyridine-2-sulfonic acid (6-methoxy-5-(2-methoxyphenoxy)-2-(pyridin-4-yl)pyrimidin-4-yl)amide

Indication

Disease Entry	ICD 11	Status	REF
Diabetic nephropathy	GB61.Z	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 9912992
  CAS Number: CAS 290815-26-8
  TTD Drug ID: DM2I8NT

Molecule-Related Drug Atlas

Drug(s) Targeting Endothelin A receptor (EDNRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[4]
Ambrisentan	DMD1QXW	Pulmonary arterial hypertension	BB01.0	Approved	[5]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[6]
Sparsentan	DMMP51W	IgA nephropathy	MF8Y	Approved	[7]
LU302146	DMMJVXZ	Pulmonary hypertension	BB01	Approved	[8]
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[9]
Clazosentan	DMQSBX4	Cerebral vasospasm	BA85.Z	Phase 3	[10]
PF-1228305	DMS1EQ7	Pulmonary hypertension	BB01	Phase 3	[11]
Darusentan	DMN8DQH	Hypotension	BA20-BA21	Phase 3	[12]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[13]

Drug(s) Affected By Follitropin subunit beta (FSHB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[14]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[15]
Goserelin	DMAT8CG	Breast cancer	2C60-2C65	Approved	[16]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[17]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[18]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[19]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[20]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[21]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[22]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[23]

Drug(s) Affected By Lutropin subunit beta (LHB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leuprorelin acetate	DM15HAT	Prostate cancer	2C82.0	Approved	[24]
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[27]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[14]
Alprazolam	DMC7XDN	Anxiety		Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Norethindrone acetate	DMDGCQP	N. A.	N. A.	Approved	[25]
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[27]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Gene/Protein Processing	[3]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Gene/Protein Processing	[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: 8260).
• [2] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [3] Influence of avosentan (SPP3OI) on the pharmacokinetics of a second generation oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers. Int J Clin Pharmacol Ther. 2006 Dec;44(12):668-74. doi: 10.5414/cpp44668.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [6] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [7] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [8] Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
• [9] Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine models of allergic asthma: demonstration of mouse strain specificity. Clin Sci (Lond). 2002 Aug;103 Suppl 48:367S-370S.
• [10] Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subar... Acta Neurochir (Wien). 2007;149(9):911-8; discussion 918.
• [11] Pfizer. Product Development Pipeline. March 31 2009.
• [12] Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
• [13] Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
• [14] Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012 Nov 1;118(21):5302-9. doi: 10.1002/cncr.27450. Epub 2012 Apr 4.
• [15] Suppression of spermatogenesis in patients with Beh?et's disease treated with cyclophosphamide and colchicine. Fertil Steril. 1981 Jul;36(1):76-80. doi: 10.1016/s0015-0282(16)45622-0.
• [16] [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1288-91.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men. Exp Clin Endocrinol Diabetes. 1999;107(1):63-9. doi: 10.1055/s-0029-1212075.
• [19] Aromatase inhibition, testosterone, and seizures. Epilepsy Behav. 2004 Apr;5(2):260-3. doi: 10.1016/j.yebeh.2003.12.001.
• [20] Male sexual dysfunction during treatment with cimetidine. Br Med J. 1979 Mar 10;1(6164):659. doi: 10.1136/bmj.1.6164.659.
• [21] Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. Psychoneuroendocrinology. 2009 Jan;34(1):129-39. doi: 10.1016/j.psyneuen.2008.08.015. Epub 2008 Oct 5.
• [22] Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab. 2000 May;85(5):1918-22. doi: 10.1210/jcem.85.5.6527.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] Erectile function and nocturnal penile tumescence in patients with prostate cancer undergoing luteinizing hormone-releasing hormone agonist therapy. Int J Urol. 1999 Jan;6(1):19-23. doi: 10.1046/j.1442-2042.1999.06128.x.
• [25] Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat. Mol Cell Endocrinol. 2010 Oct 26;328(1-2):16-21. doi: 10.1016/j.mce.2010.06.010. Epub 2010 Jun 25.
• [26] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [27] Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
• [28] The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation. J Clin Endocrinol Metab. 1995 Mar;80(3):818-23. doi: 10.1210/jcem.80.3.7883836.
• [29] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.