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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H27F3N2O6
Molecular Weight 520.4976
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TEZACAFTOR

SMILES

CC(C)(CO)C1=CC2=CC(NC(=O)C3(CC3)C4=CC=C5OC(F)(F)OC5=C4)=C(F)C=C2N1C[C@@H](O)CO

InChI

InChIKey=MJUVRTYWUMPBTR-MRXNPFEDSA-N
InChI=1S/C26H27F3N2O6/c1-24(2,13-33)22-8-14-7-18(17(27)10-19(14)31(22)11-16(34)12-32)30-23(35)25(5-6-25)15-3-4-20-21(9-15)37-26(28,29)36-20/h3-4,7-10,16,32-34H,5-6,11-13H2,1-2H3,(H,30,35)/t16-/m1/s1

HIDE SMILES / InChI

Description

Tezacaftor (VX-661) is an investigational compound developed by Vertex Pharmaceuticals to treat cystic fibrosis (CF). It is an oral corrector of the CF transmembrane regulator (CFTR) and is similar to lumacaftor, another N-aryl-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxamide derivative developed by Vertex. Cystic fibrosis is caused by defects in CFTR gene, which encodes an epithelial chloride channel. The most common mutant Δ508CFTR is a misfolded protein that does not reach the cell membrane. VX-661 corrects trafficking of Δ508CFTR and partially restores chloride channel activity. In vitro, a combination of VX-661 and ivacaftor, an FDA approved in 2012 CFTR potentiator which increases the time the CFTR channel is open, allowing chloride ions to flow through the CFTR proteins on the surface of epithelial cells, resulted in greater CFTR activity compared with VX-661 alone. In February 2012, a phase 2, double-blind, placebo-controlled study of VX-661 was initiated in CF patients who were homozygous or heterozygous for the F508del mutation. There is an ongoing Vertex Phase 3 development program of VX-661 in combination with ivacaftor which includes four studies on CF patients 1) with two copies of the F508del mutation, 2) one copy of the F508del mutation and a second mutation that results in residual CFTR function, 3) one copy of the F508del mutation and a second mutation that results in residual CFTR function gating defect in the CFTR protein and 4) one copy of the F508del mutation and a second mutation that results in minimal CFTR function.

CNS Activity

Originator

Approval Year

Target Info

Target Info

Condition Info

Condition Info

ConditionModalityTargetsHighest PhaseProduct
Primary
PMID

PMID

TitleDatePMID
CFTR Modulators for the Treatment of Cystic Fibrosis.
2014 Jul
Novel picolinamide-based cystic fibrosis transmembrane regulator modulators: evaluation of WO2013038373, WO2013038376, WO2013038381, WO2013038386 and WO2013038390.
2014 Jul
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.
2014 Jul 23
Patent

Sample Use Guides

In Vivo Use Guide
Four weeks of treatment with varying daily doses of VX-661 (10, 30, 100, or 150 mg) either as monotherapy, in combination with ivacaftor (150 mg taken every 12 hours).
Route of Administration: Oral
Name Type Language
TEZACAFTOR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
TEZACAFTOR [WHO-DD]
Common Name English
VX-661
Code English
TEZACAFTOR [USAN]
Common Name English
TEZACAFTOR [INN]
Common Name English
CYCLOPROPANECARBOXAMIDE, 1-(2,2-DIFLUORO-1,3-BENZODIOXOL-5-YL)-N-(1-((2R)-2,3-DIHYDROXYPROPYL)-6-FLUORO-2-(2-HYDROXY-1,1-DIMETHYLETHYL)-1H-INDOL-5-YL)-
Systematic Name English
Code System Code Type Description
ChEMBL
CHEMBL3544914
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY
PUBCHEM
46199646
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY SWITZERF
EPA CompTox
1152311-62-0
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY
CAS
1152311-62-0
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY
INN
10104
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY
EU-Orphan Drug
EU/3/14/1281(POSITIVE)
Created by admin on Tue Mar 06 11:56:27 UTC 2018 , Edited by admin on Tue Mar 06 11:56:27 UTC 2018
PRIMARY On 4 July 2014, orphan designation (EU/3/14/1281) was granted by the European Commission to Vertex Pharmaceuticals (UK) Limited, United Kingdom, for 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl}cyclopropanecarboxamide (tezacaftor) for the treatment of cystic fibrosis. This medicine is now known as tezacaftor.