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Details

Stereochemistry ABSOLUTE
Molecular Formula C14H7Cl2NO3.C7H17NO5
Molecular Weight 503.33
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TAFAMIDIS MEGLUMINE

SMILES

CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)C1=CC2=C(C=C1)N=C(O2)C3=CC(Cl)=CC(Cl)=C3

InChI

InChIKey=DQJDBUPLRMRBAB-WZTVWXICSA-N
InChI=1S/C14H7Cl2NO3.C7H17NO5/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13;1-8-2-4(10)6(12)7(13)5(11)3-9/h1-6H,(H,18,19);4-13H,2-3H2,1H3/t;4-,5+,6+,7+/m.0/s1

HIDE SMILES / InChI

Molecular Formula C7H17NO5
Molecular Weight 195.2136
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C14H7Cl2NO3
Molecular Weight 308.116
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Familial amyloid polyneuropathy: new developments in genetics and treatment.
1996 Oct
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
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).
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:57:58 UTC 2019
Edited
by admin
on Mon Oct 21 20:57:58 UTC 2019
Record UNII
ZU7CF08A1A
Record Status Validated (UNII)
Record Version
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Name Type Language
TAFAMIDIS MEGLUMINE
DASH   USAN   WHO-DD  
USAN  
Official Name English
TAFAMIDIS MEGLUMINE [MI]
Common Name English
TAFAMIDIS MEGLUMINE [WHO-DD]
Common Name English
D-GLUCO-2,3,4,5,6-PENTAHYDROXY-N-METHYLHEXAN-1-AMINIUM 2-(3,5-DICHLOROPHENYL)BENZOXAZOLE-6-CARBOXYLATE
Common Name English
VYNDAQEL
Brand Name English
TAFAMIDIS MEGLUMINE [USAN]
Common Name English
TAFAMIDIS MEGLUMINE [JAN]
Common Name English
FX-1006A
Code English
D-GLUCITOL, 1-DEOXY-1-(METHYLAMINO)-, 2-(3,5-DICHLOROPHENYL)-6-BENZOXAZOLECARBOXYLATE (1:1)
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 363312
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
NCI_THESAURUS C87006
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
EU-Orphan Drug EU/3/06/401
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL2103837
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
NCI_THESAURUS
C84194
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
RXCUI
1727003
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY RxNorm
PUBCHEM
24970412
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
EVMPD
SUB31457
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
JAPANESE REVIEW
VYNDAQEL
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY APPROVED SEPTEMBER 2013
CAS
951395-08-7
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
MERCK INDEX
M11717
Created by admin on Mon Oct 21 20:57:58 UTC 2019 , Edited by admin on Mon Oct 21 20:57:58 UTC 2019
PRIMARY
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