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

General Information of Drug (ID: DMJBXO3)

• Drug Name: VX-661 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 46199646
  CAS Number: CAS 1152311-62-0
  TTD Drug ID: DMJBXO3
  VARIDT Drug ID: DR01157
  INTEDE Drug ID: DR1571

Molecule-Related Drug Atlas

Drug(s) Targeting cAMP-dependent chloride channel (CFTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ivacaftor	DMZC1HS	Cystic fibrosis	CA25	Approved	[4]
Crofelemer	DM4AMQZ	HIV-associated diarrhoea	1A2Z	Approved	[5]
Tezacaftor and ivacaftor	DMY62FC	Acute lung injury	NB32.3	Approved	[6]
ABBV-2222	DM4ZLTY	Cystic fibrosis	CA25	Phase 2	[7]
GLPG-1837	DMOCRYB	Cystic fibrosis	CA25	Phase 2	[7]
iOWH032	DM5TMYC	Diarrhea	ME05.1	Phase 2	[8]
Lumacaftor	DMCLWDJ	Cystic fibrosis	CA25	Phase 2	[9]
QBW251	DMQ5APT	Chronic obstructive pulmonary disease	CA22	Phase 2	[10]
ABBV-3067	DMB01L5	Cystic fibrosis	CA25	Phase 1	[7]
ABBV-2737	DMU6K37	Cystic fibrosis	CA25	Phase 1	[7]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[14]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
cAMP-dependent chloride channel (CFTR)	TTRLZHP	CFTR_HUMAN	Regulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A5 (CYP3A5) Main DME	DEIBDNY	CP3A5_HUMAN	Substrate	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11.
• [3] Pharmacokinetic and drug-drug interaction profiles of the combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [6] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [7] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [8] Developing novel antisecretory drugs to treat infectious diarrhea. Future Med Chem. 2011 Aug;3(10):1317-25.
• [9] A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38.
• [10] Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). J Cyst Fibros. 2021 Mar;20(2):250-256.
• [11] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [12] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [13] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [14] Drug Interactions Flockhart Table
• [15] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [16] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [17] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [18] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [19] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.