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Details

Stereochemistry ACHIRAL
Molecular Formula C14H7Cl2NO3
Molecular Weight 308.116
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TAFAMIDIS

SMILES

OC(=O)C1=CC=C2N=C(OC2=C1)C3=CC(Cl)=CC(Cl)=C3

InChI

InChIKey=TXEIIPDJKFWEEC-UHFFFAOYSA-N
InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)

HIDE SMILES / InChI

Description

Tafamidis meglumine (Vyndaqel®, Pfizer) is a novel, first-in-class drug for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare neurodegenerative disorder characterized by progressive sensory, motor and autonomic impairment that is ultimately fatal. Pathogenic mutations in the transthyretin (TTR) protein lead to destabilization of its tetrameric structure and subsequent formation of amyloid aggregates. Tafamidis is a small-molecule inhibitor that binds selectively to TTR in human plasma and kinetically stabilizes the tetrameric structure of both wild-type TTR and a number of different mutants. Clinical trials indicate that tafamidis slows disease progression in patients with TTR-FAP and reduces the burden of disease, demonstrating improvement in small and large nerve fiber function, modified body mass index and lower extremity neurological examination. Tafamidis meglumine has been launched for TTR FAP in the EU, Japan, Argentina, Malta and Mexico, and is preregistration in the US for this indication.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.0 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Vyndaqel
PubMed

PubMed

TitleDatePubMed
A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves.
1952 Sep
Fibril in senile systemic amyloidosis is derived from normal transthyretin.
1990 Apr
Familial amyloid polyneuropathy: new developments in genetics and treatment.
1996 Oct
Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.
1997 Feb 13
Autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).
1998 Dec
Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha.
1999 Jul 14
The pathway by which the tetrameric protein transthyretin dissociates.
2005 Nov 29
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade.
2012 Jun 12
AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin.
2013 Jun 11
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose of tafamidis meglumine is 20 mg orally once daily.
Route of Administration: Oral
In Vitro Use Guide
Tafamidis effectively inhibited fibril formation induced by acid denaturation in a concentration-dependent manner with similar potency for wild-type TTR, V30M TTR and V122I TTR, reaching its EC50 at a tafamidis:TTR stoichiometry of <1 (EC50 was in the range of 2.7-3.2 uM, corresponding to a tafamidis: TTR stoichiometry range of 0.75-0.9).
Name Type Language
TAFAMIDIS
INN   MART.   USAN   WHO-DD  
USAN   INN  
Official Name English
FX006
Code English
FX1006
Code English
FX-1006
Code English
2-(3,5-DICHLOROPHENYL)BENZOXAZOLE-6-CARBOXYLIC ACID
Systematic Name English
TAFAMIDIS [WHO-DD]
Common Name English
6-BENZOXAZOLECARBOXYLIC ACID, 2-(3,5-DICHLOROPHENYL)-
Common Name English
TAFAMIDIS [MART.]
Common Name English
TAFAMIDIS [MI]
Common Name English
FX-1005
Code English
FX-006
Code English
TAFAMIDIS [INN]
Common Name English
TAFAMIDIS [USAN]
Common Name English
Classification Tree Code System Code
WHO-ATC N07XX08
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
WHO-VATC QN07XX08
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
Code System Code Type Description
EVMPD
SUB33016
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
MESH
C547076
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
EPA CompTox
594839-88-0
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
ChEMBL
CHEMBL2103837
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
MERCK INDEX
M11717
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
IUPHAR
8378
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
INN
9094
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
RXCUI
1545063
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY RxNorm
WIKIPEDIA
TAFAMIDIS
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
NCI_THESAURUS
C84193
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY
PUBCHEM
11001318
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY SWITZERF
CAS
594839-88-0
Created by admin on Tue Mar 06 10:46:30 UTC 2018 , Edited by admin on Tue Mar 06 10:46:30 UTC 2018
PRIMARY