U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C26H27F3N2O6
Molecular Weight 520.4986
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TEZACAFTOR

SMILES

CC(C)(CO)c1cc2cc(c(cc2n1C[C@]([H])(CO)O)F)NC(=O)C3(CC3)c4ccc5c(c4)OC(F)(F)O5

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

Molecular Formula C26H27F3N2O6
Molecular Weight 520.4986
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=984388

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.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
SYMDEKO

Approved Use

SYMDEKO is a combination of tezacaftor and ivacaftor, indicated for the treatment of patients with cystic fibrosis (CF) aged 12 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

Launch Date

1518307200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.95 μg/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: IVACAFTOR
TEZACAFTOR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
15000 ng/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEZACAFTOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
84.5 μg × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: IVACAFTOR
TEZACAFTOR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
225000 ng × h/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEZACAFTOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6260 ng*h/mL
10 mg 1 times / day steady, oral
dose: 10 mg
route of administration: oral
experiment type: steady
co-administered:
TEZACAFTOR plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
98900 ng*h/mL
150 mg 1 times / day steady, oral
dose: 150 mg
route of administration: oral
experiment type: steady
co-administered:
TEZACAFTOR plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: IVACAFTOR
TEZACAFTOR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
83.23 h
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEZACAFTOR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: IVACAFTOR
TEZACAFTOR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Other AEs: Headache...
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Disc. AE: Transaminases increased...
Other AEs: Nausea, Sinus congestion...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (0.2%)
Other AEs:
Nausea (9%)
Sinus congestion (4%)
Dizziness (4%)
Sources:
300 mg 1 times / day multiple, oral
Studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
healthy
AEs

AEs

AESignificanceDosePopulation
Headache 15%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Transaminases increased 0.2%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Dizziness 4%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Sinus congestion 4%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
Nausea 9%
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, >12 years
Health Status: unhealthy
Age Group: >12 years
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
weak [Ki 11.65 uM]
weak [Ki 12.5 uM]
weak [Ki 13 uM]
weak [Ki 13.5 uM]
weak [Ki 21.2 uM]
weak [Ki 22.5 uM]
weak [Ki 24.4 uM]
weak [Ki 6.05 uM]
weak [Ki 7 uM]
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:09:45 UTC 2021
Edited
by admin
on Sat Jun 26 08:09:45 UTC 2021
Record UNII
8RW88Y506K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TEZACAFTOR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
TEZACAFTOR [ORANGE BOOK]
Common Name English
SYMKEVI COMPONENT TEZACAFTOR
Brand Name English
TEZACAFTOR COMPONENT OF TRIKAFTA
Brand Name English
TEZACAFTOR [WHO-DD]
Common Name English
VX-661
Code English
TEZACAFTOR [USAN]
Common Name English
TRIKAFTA COMPONENT TEZACAFTOR
Brand 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
TEZACAFTOR [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 577517
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
WHO-ATC R07AX31
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
FDA ORPHAN DRUG 427414
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
EU-Orphan Drug EU/3/18/2116
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
NCI_THESAURUS C87006
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
FDA ORPHAN DRUG 777220
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
FDA ORPHAN DRUG 638618
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
FDA ORPHAN DRUG 647618
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C152581
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
DRUG CENTRAL
5276
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL3544914
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
RXCUI
1999382
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
LACTMED
Elexacaftor, Tezacaftor and Ivacaftor
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
EVMPD
SUB188271
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
FDA UNII
8RW88Y506K
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
DRUG BANK
DB11712
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
PUBCHEM
46199646
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
EPA CompTox
1152311-62-0
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
MERCK INDEX
M12033
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
CAS
1152311-62-0
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
INN
10104
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
LACTMED
Tezacaftor and Ivacaftor
Created by admin on Sat Jun 26 08:09:45 UTC 2021 , Edited by admin on Sat Jun 26 08:09:45 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
URINE
INHIBITOR OF AGGREGATION->TARGET
helps with the trafficking of the CFTR protein to the epithelial surface
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
BINDER->LIGAND
tezacaftor are approximately 99% bound to plasma proteins, primarily to albumin.
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC