bamocaftor   Click here for help

GtoPdb Ligand ID: 10553

Synonyms: compound 1 [WO2018064632A1] | VX-659 | VX659
Compound class: Synthetic organic
Comment: Bamocaftor (VX-659) is a next-generation CFTR corrector class molecule [2]. It is structurally related to elexacaftor and like other corrector molecules was designed to improve CFTR protein processing and trafficking in the presence of the F508del mutation. Bamocaftor's mechanism of action is different from that of the first generation CFTR corrector tezacaftor and its functional and clinical effects appear to be additive [2]. As such a triple combination therapeutic with tezacaftor, izacaftor (a CFTR potentiator that increases CFTR channel gating activity) and bamocaftor increases CFTR function beyond that achieved by current standard of care dual therapy tezacaftor/izacaftor, and improves clinical symptoms in patients with cystic fibrosis with one or two F508del alleles [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 114.28
Molecular weight 591.21
XLogP 7.56
No. Lipinski's rules broken 1
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Canonical SMILES CC1CN(C(C1)(C)C)c1nc(ccc1C(=O)NS(=O)(=O)c1ccccc1)n1ccc(n1)OCCC1(CC1)C(F)(F)F
Isomeric SMILES C[C@@H]1CN(C(C1)(C)C)c1nc(ccc1C(=O)NS(=O)(=O)c1ccccc1)n1ccc(n1)OCCC1(CC1)C(F)(F)F
InChI InChI=1S/C28H32F3N5O4S/c1-19-17-26(2,3)35(18-19)24-21(25(37)34-41(38,39)20-7-5-4-6-8-20)9-10-22(32-24)36-15-11-23(33-36)40-16-14-27(12-13-27)28(29,30)31/h4-11,15,19H,12-14,16-18H2,1-3H3,(H,34,37)/t19-/m0/s1
1. Alcacio T, Baek M, Grootenhuis P, Hadida Ruah SS, Hughes RM, Keshavarz-Shokri A, McAuley-Aoki R, McCartney J, Miller MT, Van Goor F et al.. (2018)
Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator.
Patent number: WO2018064632A1. Assignee: Vertex Pharmaceuticals. Priority date: 30/09/2016. Publication date: 05/04/2018.
2. Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL et al.. (2018)
VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
N Engl J Med, 379 (17): 1599-1611. [PMID:30334693]
3. Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM et al.. (2019)
Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial.
Lancet, 394 (10212): 1940-1948. [PMID:31679946]