Tafamidis Free Acid | CAS#594839-88-0 | CAS#951395-08-7 | Transthyretin Protein Stabilizer

MedKoo Cat#: 319842 | Name: Tafamidis

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tafamidis, Tafamidis, also known as Fx-1006 or PF-06291826, is a drug for the amelioration of transthyretin-related hereditary amyloidosis (also familial amyloid polyneuropathy, or FAP), a rare but deadly neurodegenerative disease. The drug was approved by the European Medicines Agency in November 2011 and by the Japanese Pharmaceuticals and Medical Devices Agency in September 2013. Tafamidis functions by kinetic stabilization of the correctly folded tetrameric form of the transthyretin (TTR) protein.

Chemical Structure

Tafamidis

CAS#594839-88-0 (free acid)

Theoretical Analysis

MedKoo Cat#: 319842

Name: Tafamidis

CAS#: 594839-88-0 (free acid)

Chemical Formula: C14H7Cl2NO3

Exact Mass: 306.9803

Molecular Weight: 308.11

Elemental Analysis: C, 54.58; H, 2.29; Cl, 23.01; N, 4.55; O, 15.58

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,350.00	Ready to ship
1g	USD 2,350.00	Ready to ship
2g	USD 3,950.00	Ready to ship

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Related CAS #

594839-88-0 (free acid) 951395-08-7 (meglumine)

Synonym

Fx-1006, Fx1006, Fx 1006, Fx-1006A; PF-06291826; PF06291826; PF 06291826; Tafamidis; Vyndaqel

IUPAC/Chemical Name

2-(3,5-dichlorophenyl)benzo[d]oxazole-6-carboxylic acid

InChi Key

TXEIIPDJKFWEEC-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A9T01K22

QC Data

View QC data: current batch, Lot#A9T01K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Tafamidis is a kinetic stabilizer of transthyretin (TTR) that prevents amyloidogenesis by wild-type and mutant TTRs.

In vitro activity:

At a ligand:TTR tetramer molar ratio of 0.5:1, mds84 tafamidis reduced fibril formation by 40%. At molar equivalence, inhibition increased at 60% with tafamidis. At twofold and greater molar excess of ligand, both monovalent ligands, tafamidis inhibited TTR fibrillogenesis by the same amount (~90%) as mds84. Reference: Sci Rep. 2017 Mar 15;7(1):182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428290/

In vivo activity:

Tafamidis, a novel drug to treat transthyretin-related amyloidosis, was studied in rats after intravenous and oral administration at doses of 0.3-3 mg/kg. After intravenous injection, systemic clearance (CL), volumes of distribution at steady state (Vss) and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 6.41-7.03 mL/h/kg, 270-354 mL/kg and 39.5-46.9 h, respectively. Following oral administration, absolute bioavailability was 99.7-104% and was independent of doses from 0.3 to 3 mg/kg. In the urine and faeces, 4.36% and 48.9% of tafamidis, respectively, were recovered. Tafamidis was distributed primarily in the liver and not in the brain, kidney, testis, heart, spleen, lung, gut, muscle, or adipose tissue. Further, tafamidis was very stable in rat liver microsomes, and its plasma protein binding was 99.9%. Reference: Xenobiotica. 2018 Aug;48(8):831-838. https://www.tandfonline.com/doi/full/10.1080/00498254.2017.1366575

	Solvent	mg/mL	mM
Solubility
	DMSO	37.5	121.71

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 308.11 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Verona G, Mangione PP, Raimondi S, Giorgetti S, Faravelli G, Porcari R, Corazza A, Gillmore JD, Hawkins PN, Pepys MB, Taylor GW, Bellotti V. Inhibition of the mechano-enzymatic amyloidogenesis of transthyretin: role of ligand affinity, binding cooperativity and occupancy of the inner channel. Sci Rep. 2017 Mar 15;7(1):182. doi: 10.1038/s41598-017-00338-x. PMID: 28298647; PMCID: PMC5428290. 2. Lee KR, Jeong JW, Hyun HC, Jang E, Ahn S, Choi S, Joo SH, Kim S, Koo TS. Pharmacokinetics of tafamidis, a transthyretin amyloidosis drug, in rats. Xenobiotica. 2018 Aug;48(8):831-838. doi: 10.1080/00498254.2017.1366575. Epub 2017 Nov 16. PMID: 28803538.

In vitro protocol:

In vivo protocol:

1. Lee KR, Jeong JW, Hyun HC, Jang E, Ahn S, Choi S, Joo SH, Kim S, Koo TS. Pharmacokinetics of tafamidis, a transthyretin amyloidosis drug, in rats. Xenobiotica. 2018 Aug;48(8):831-838. doi: 10.1080/00498254.2017.1366575. Epub 2017 Nov 16. PMID: 28803538.

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