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

General Information of Drug (ID: DMCLWDJ)

• Drug Name: Lumacaftor Drug Info
• Synonyms: VRT-325; VRT-422; VRT-532; VX-809

Indication

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 16678941
  ChEBI ID: CHEBI:90951
  CAS Number: CAS 936727-05-8
  TTD Drug ID: DMCLWDJ
  VARIDT Drug ID: DR01156

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]
VX-661	DMJBXO3	Cystic fibrosis	CA25	Phase 3	[7]
ABBV-2222	DM4ZLTY	Cystic fibrosis	CA25	Phase 2	[8]
GLPG-1837	DMOCRYB	Cystic fibrosis	CA25	Phase 2	[8]
iOWH032	DM5TMYC	Diarrhea	ME05.1	Phase 2	[9]
QBW251	DMQ5APT	Chronic obstructive pulmonary disease	CA22	Phase 2	[10]
ABBV-3067	DMB01L5	Cystic fibrosis	CA25	Phase 1	[8]
ABBV-2737	DMU6K37	Cystic fibrosis	CA25	Phase 1	[8]

Drug(s) Affected By Cystic fibrosis transmembrane conductance regulator (CFTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ivacaftor	DMZC1HS	Cystic fibrosis	CA25	Approved	[11]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Miglustat	DM5J64S	Niemann-Pick disease type C		Approved	[15]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[16]
Milrinone	DM8TUPF	Congestive heart failure	BD10	Approved	[13]
Oxidized glutathione	DM9EQC0	Breast cancer	2C60-2C65	Approved	[17]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]

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 Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Protein Interaction/Cellular Processes	[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: 7481).
• [2] 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.
• [3] Novel Therapy of Bicarbonate, Glutathione, and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport. Am J Respir Cell Mol Biol. 2020 Sep;63(3):362-373. doi: 10.1165/rcmb.2019-0287OC.
• [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] CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11.
• [8] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [9] Developing novel antisecretory drugs to treat infectious diarrhea. Future Med Chem. 2011 Aug;3(10):1317-25.
• [10] Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). J Cyst Fibros. 2021 Mar;20(2):250-256.
• [11] Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells. Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):410-8. doi: 10.1165/rcmb.2002-0247OC. Epub 2003 Apr 24.
• [14] Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids. Am J Respir Cell Mol Biol. 2004 Sep;31(3):351-7. doi: 10.1165/rcmb.2002-0086OC. Epub 2004 Jun 10.
• [15] Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622. J Pharmacol Exp Ther. 2008 Apr;325(1):89-99. doi: 10.1124/jpet.107.134502. Epub 2008 Jan 29.
• [16] Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004. J Membr Biol. 2003 Jul 15;194(2):109-17. doi: 10.1007/s00232-003-2030-z.
• [17] Reversible silencing of CFTR chloride channels by glutathionylation. J Gen Physiol. 2005 Feb;125(2):127-41. doi: 10.1085/jgp.200409115. Epub 2005 Jan 18.
• [18] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.