Details of the Drug

General Information of Drug (ID: DMCLWDJ)

Drug Name
Lumacaftor
Synonyms VRT-325; VRT-422; VRT-532; VX-809
Indication
Disease Entry ICD 11 Status REF
Cystic fibrosis CA25 Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 452.4
Logarithm of the Partition Coefficient (xlogp) 4.4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4 h []
Clearance
The clearance of drug is 2.38 L/h []
Elimination
51 of drug is primarily excreted unchanged in the feces, and only a minimal amount of the parent compound and its metabolites are excreted in the urine []
Half-life
The concentration or amount of drug in body reduced by one-half in 26 hours []
Vd
The volume of distribution (Vd) of drug is 86.0 L []
Chemical Identifiers
Formula
C24H18F2N2O5
IUPAC Name
3-[6-[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]-3-methylpyridin-2-yl]benzoic acid
Canonical SMILES
CC1=C(N=C(C=C1)NC(=O)C2(CC2)C3=CC4=C(C=C3)OC(O4)(F)F)C5=CC(=CC=C5)C(=O)O
InChI
InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)
InChIKey
UFSKUSARDNFIRC-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
16678941
ChEBI ID
CHEBI:90951
CAS Number
936727-05-8
DrugBank ID
DB09280
TTD ID
D0X0CB
VARIDT ID
DR01156
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lumacaftor (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Major Increased metabolism of Lumacaftor caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [4]
Gilteritinib DMTI0ZO Major Accelerated clearance of Lumacaftor due to the transporter induction by Gilteritinib. Acute myeloid leukaemia [2A60] [4]
Oliceridine DM6MDCF Major Increased metabolism of Lumacaftor caused by Oliceridine mediated induction of CYP450 enzyme. Acute pain [MG31] [5]
Erdafitinib DMI782S Major Increased metabolism of Lumacaftor caused by Erdafitinib mediated induction of CYP450 enzyme. Bladder cancer [2C94] [4]
HKI-272 DM6QOVN Major Increased metabolism of Lumacaftor caused by HKI-272 mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [6]
LY2835219 DM93VBZ Major Increased metabolism of Lumacaftor caused by LY2835219 mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [7]
Esterified estrogens DM9KZDO Moderate Increased metabolism of Lumacaftor caused by Esterified estrogens mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [8]
Alpelisib DMEXMYK Major Increased metabolism of Lumacaftor caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [9]
PF-04449913 DMSB068 Major Increased metabolism of Lumacaftor caused by PF-04449913 mediated induction of CYP450 enzyme. Chronic myelomonocytic leukaemia [2A40] [4]
Levonorgestrel DM1DP7T Major Increased metabolism of Lumacaftor caused by Levonorgestrel mediated induction of CYP450 enzyme. Contraceptive management [QA21] [9]
Osilodrostat DMIJC9X Major Increased metabolism of Lumacaftor caused by Osilodrostat mediated induction of CYP450 enzyme. Cushing syndrome [5A70] [4]
Bay 80-6946 DMLOS5R Major Increased metabolism of Lumacaftor caused by Bay 80-6946 mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [4]
Tazemetostat DMWP1BH Major Increased metabolism of Lumacaftor caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [10]
Ripretinib DM958QB Major Increased metabolism of Lumacaftor caused by Ripretinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [11]
Avapritinib DMK2GZX Major Increased metabolism of Lumacaftor caused by Avapritinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [9]
MK-1439 DM215WE Major Increased metabolism of Lumacaftor caused by MK-1439 mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [12]
Fostemsavir DM50ILT Major Increased metabolism of Lumacaftor caused by Fostemsavir mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [4]
TP-434 DM5A31S Major Increased metabolism of Lumacaftor caused by TP-434 mediated induction of CYP450 enzyme. Infectious gastroenteritis/colitis [1A40] [4]
Pemigatinib DM819JF Major Increased metabolism of Lumacaftor caused by Pemigatinib mediated induction of CYP450 enzyme. Liver cancer [2C12] [4]
Brigatinib DM7W94S Major Increased metabolism of Lumacaftor caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [6]
Lurbinectedin DMEFRTZ Major Decreased metabolism of Lumacaftor caused by Lurbinectedin mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [13]
PF-06463922 DMKM7EW Major Increased metabolism of Lumacaftor caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [9]
Osimertinib DMRJLAT Major Increased metabolism of Lumacaftor caused by Osimertinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [6]
Pralsetinib DMWU0I2 Major Increased metabolism of Lumacaftor caused by Pralsetinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [4]
Capmatinib DMYCXKL Major Increased metabolism of Lumacaftor caused by Capmatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [7]
Selpercatinib DMZR15V Major Increased metabolism of Lumacaftor caused by Selpercatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [4]
Acalabrutinib DM7GCVW Major Increased metabolism of Lumacaftor caused by Acalabrutinib mediated induction of CYP450 enzyme. Mature B-cell lymphoma [2A85] [14]
Selumetinib DMC7W6R Major Increased metabolism of Lumacaftor caused by Selumetinib mediated induction of CYP450 enzyme. Melanoma [2C30] [15]
LGX818 DMNQXV8 Major Increased metabolism of Lumacaftor caused by LGX818 mediated induction of CYP450 enzyme. Melanoma [2C30] [16]
Ubrogepant DM749I3 Major Increased metabolism of Lumacaftor caused by Ubrogepant mediated induction of CYP450 enzyme. Migraine [8A80] [4]
Rimegepant DMHOAUG Major Increased metabolism of Lumacaftor caused by Rimegepant mediated induction of CYP450 enzyme. Migraine [8A80] [17]
Siponimod DM2R86O Major Increased metabolism of Lumacaftor caused by Siponimod mediated induction of CYP450 enzyme. Multiple sclerosis [8A40] [6]
Deflazacort DMV0RNS Major Increased metabolism of Lumacaftor caused by Deflazacort mediated induction of CYP450 enzyme. Muscular dystrophy [8C70] [9]
Rolapitant DM8XP26 Major Increased metabolism of Lumacaftor caused by Rolapitant mediated induction of CYP450 enzyme. Nausea/vomiting [MD90] [9]
Entrectinib DMMPTLH Major Increased metabolism of Lumacaftor caused by Entrectinib mediated induction of CYP450 enzyme. Non-small cell lung cancer [2C25] [9]
S-297995 DM26IH8 Major Increased metabolism of Lumacaftor caused by S-297995 mediated induction of CYP450 enzyme. Opioid use disorder [6C43] [4]
Istradefylline DM20VSK Major Increased metabolism of Lumacaftor caused by Istradefylline mediated induction of CYP450 enzyme. Parkinsonism [8A00] [4]
Macimorelin DMQYJIR Moderate Increased metabolism of Lumacaftor caused by Macimorelin mediated induction of CYP450 enzyme. Pituitary gland disorder [5A60-5A61] [18]
Lefamulin DME6G97 Major Accelerated clearance of Lumacaftor due to the transporter induction by Lefamulin. Pneumonia [CA40] [4]
Darolutamide DMV7YFT Major Increased metabolism of Lumacaftor caused by Darolutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [7]
Upadacitinib DM32B5U Major Increased metabolism of Lumacaftor caused by Upadacitinib mediated induction of CYP450 enzyme. Rheumatoid arthritis [FA20] [4]
Tedizolid DMG2SKR Moderate Decreased clearance of Lumacaftor due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [9]
Larotrectinib DM26CQR Major Increased metabolism of Lumacaftor caused by Larotrectinib mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [6]
Pitolisant DM8RFNJ Major Increased metabolism of Lumacaftor caused by Pitolisant mediated induction of CYP450 enzyme. Somnolence [MG42] [9]
Fostamatinib DM6AUHV Major Increased metabolism of Lumacaftor caused by Fostamatinib mediated induction of CYP450 enzyme. Thrombocytopenia [3B64] [4]
As-1670542 DMV05SW Moderate Increased metabolism of Lumacaftor caused by As-1670542 mediated induction of CYP450 enzyme. Thrombocytopenia [3B64] [9]
⏷ Show the Full List of 46 DDI Information of This Drug

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 Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
5 Product Information. Mycobutin (rifabutin). Pharmacia and Upjohn, Kalamazoo, MI.
6 Cerner Multum, Inc. "Australian Product Information.".
7 Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
8 Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61. [PMID: 7009137]
9 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
10 Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
11 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
12 Product Information. Pifeltro (doravirine). Merck &amp Company Inc, Whitehouse Station, NJ.
13 Product Information. Xermelo (telotristat ethyl). Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
14 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
15 Multum Information Services, Inc. Expert Review Panel.
16 Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
17 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
18 Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.