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

General Information of Drug (ID: DM4YDAJ)

• Drug Name: Sildenafil Drug Info
• Synonyms: sildenafil; 139755-83-2; VIAGRA; Sildenafil [INN:BAN]; UK-92480; UNII-3M7OB98Y7H; UK-92,480-10; C22H30N6O4S; HSDB 7305; CHEMBL192; UK 92480-10; CHEBI:9139; 3M7OB98Y7H; BNRNXUUZRGQAQC-UHFFFAOYSA-N; Sildenafil

Indication

Disease Entry	ICD 11	Status	REF
Alveolar capillary dysplasia with misalignment of pulmonary veins		Approved	[1]
Erectile dysfunction	HA01.1	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[3]
Respiratory failure	CB41	Investigative	[1]

• Therapeutic Class: Antiviral Agents
• Cross-matching ID:
  PubChem CID: 135398744
  ChEBI ID: CHEBI:9139
  CAS Number: CAS 139755-83-2
  TTD Drug ID: DM4YDAJ
  ACDINA Drug ID: D00622

Molecule-Related Drug Atlas

Drug(s) Affected By Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[7]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[8]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[9]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[10]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[11]
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[13]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[14]
Sibutramine	DMFJTDI	Obesity	5B81	Approved	[15]
Almogran	DM7I64Z	Migraine	8A80	Approved	[16]

Drug(s) Affected By Angiotensin-converting enzyme (ACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[17]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[17]
Quinapril	DMR8H31	Chronic heart failure	BD1Z	Approved	[17]
Cilazapril	DM4V6JA	Congestive heart failure	BD10	Approved	[18]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[19]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[20]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[9]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[22]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
HUMAN phosphodiesterase type 5 (PDE5)	TTRYFSB	PDE5A_HUMAN	Inhibitor	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Drug Response	[5]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Drug Response	[6]

References

• [1] Sildenafil FDA Label
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 206401.
• [3] ClinicalTrials.gov (NCT04304313) A Pilot Study of Sildenafil in COVID-19. U.S. National Institutes of Health.
• [4] Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9. doi: 10.1128/JVI.79.3.1966-1969.2005.
• [5] ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction. Urology. 2003 Jul;62(1):152-7. doi: 10.1016/s0090-4295(03)00137-7.
• [6] Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study. J Urol. 2003 Mar;169(3):1048-51. doi: 10.1097/01.ju.0000058369.72348.ba.
• [7] G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. Pharmacogenomics. 2008 Oct;9(10):1429-36. doi: 10.2217/14622416.9.10.1429.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] 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.
• [11] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Int J Neuropsychopharmacol. 2003 Dec;6(4):339-46. doi: 10.1017/S1461145703003663.
• [15] Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet Genomics. 2009 Sep;19(9):730-3. doi: 10.1097/FPC.0b013e3283307cf1.
• [16] G protein beta3 polymorphism and triptan response in cluster headache. Clin Pharmacol Ther. 2007 Oct;82(4):396-401. doi: 10.1038/sj.clpt.6100159. Epub 2007 Mar 14.
• [17] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [18] [A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):581-4.
• [19] ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant. 2000 Oct;15(10):1617-23. doi: 10.1093/ndt/15.10.1617.
• [20] Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates. J Am Chem Soc. 2012 Feb 22;134(7):3396-410. doi: 10.1021/ja208791f. Epub 2012 Feb 10.
• [21] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [22] "Crack" cocaine-induced syndrome mimicking sarcoidosis. Am J Med Sci. 1999 Jun;317(6):416-8. doi: 10.1097/00000441-199906000-00011.
• [23] Nicotine induced changes in gene expression by human coronary artery endothelial cells. Atherosclerosis. 2001 Feb 1;154(2):277-83.