Tafamidis

• CAT Number: I004229
• CAS Number: 594839-88-0
• Molecular Formula: C14H7Cl2NO3
• Molecular Weight: 308.1
• Purity: ≥95%
• Synonyms: PF-06291826
• Target: Transthyretin (TTR)
• Solubility: DMSO: ≥ 54 mg/mL
• Storage: -20°C
• IUPAC Name: 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid
• InChI: 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)
• InChIKey: TXEIIPDJKFWEEC-UHFFFAOYSA-N
• SMILES: C1=CC2=C(C=C1C(=O)O)OC(=N2)C3=CC(=CC(=C3)Cl)Cl

Tafamidis(CAT: I004229) is a medication used for the treatment of transthyretin amyloidosis (ATTR), a rare genetic disease characterized by the buildup of abnormal protein deposits in various organs. Tafamidis specifically targets and stabilizes the tetrameric form of the transthyretin (TTR), a protein involved in the transport of thyroid hormone and retinol-binding protein. By stabilizing the TTR tetramer, tafamidis helps prevent the misfolding and aggregation of TTR into amyloid fibrils, which are responsible for organ damage in ATTR. Tafamidis has shown efficacy in slowing disease progression, reducing neurological deterioration, and improving quality of life in patients with ATTR.

Overview of Clinical Research

Tafamidis is an Amyloid inhibitor. It has been granted for the orphan drug status in Amyloid polyneuropathy and Cardiomyopathies. The phase-I clinical trials in Cardiomyopathies (In volunteers) in USA (PO) (NCT04575116) initated in Sep 2020.

Reference

1:Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Keohane D, Schwartz J, Gundapaneni B, Stewart M, Amass L.Amyloid. 2017 Apr 10:1-7. doi: 10.1080/13506129.2017.1301419. [Epub ahead of print] PMID: 28393570
2:Treatment of transthyretin familial amyloid polyneuropathy with tafamidis: a case report. Miyazaki Y.Nihon Ronen Igakkai Zasshi. 2017;54(1):75-80. doi: 10.3143/geriatrics.54.75. PMID: 28202889 Free Article
3:Tafamidis for the Treatment of Hereditary Transthyretin Amyloid Cardiomyopathy: A Case Report. Fujita T, Inomata T, Kaida T, Iida Y, Ikeda Y, Nabeta T, Ishii S, Maekawa E, Naruke T, Koitabashi T, Kitamura E, Sekijima Y, Ako J.Cardiology. 2017;137(2):74-77. doi: 10.1159/000455089. Epub 2017 Feb 3. PMID: 28152524
4:Development and validation of a liquid chromatography-tandem mass spectrometry method for the assay of tafamidis in rat plasma: Application to a pharmacokinetic study in rats. Hyun HC, Jeong JW, Kim HR, Oh JH, Lee JH, Choi S, Kim YS, Koo TS.J Pharm Biomed Anal. 2017 Apr 15;137:90-95. doi: 10.1016/j.jpba.2017.01.020. Epub 2017 Jan 10. PMID: 28107689
5:Tafamidis Meglumine — Benefit Assessment According to §35a Social Code Book V [Internet]. Institute for Quality and Efficiency in Health Care.Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2012 Mar 13. PMID: 27905733 Free Books & Documents
6:Long-term treatment of transthyretin familial amyloid polyneuropathy with tafamidis: a clinical and neurophysiological study. Planté-Bordeneuve V, Gorram F, Salhi H, Nordine T, Ayache SS, Le Corvoisier P, Azoulay D, Feray C, Damy T, Lefaucheur JP.J Neurol. 2017 Feb;264(2):268-276. doi: 10.1007/s00415-016-8337-3. Epub 2016 Nov 22. PMID: 27878441
7:Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy. Waddington Cruz M, Amass L, Keohane D, Schwartz J, Li H, Gundapaneni B.Amyloid. 2016 Sep;23(3):178-183. Epub 2016 Aug 5. PMID: 27494299 Free PMC Article
8:Tafamidis in hereditary ATTR amyloidosis – our experience on monitoring the ocular manifestations. Casal I, Monteiro S, Beirão JM.Amyloid. 2016 Dec;23(4):262-263. Epub 2016 Oct 17. No abstract available. PMID: 27748624
9:Erratum to: Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area. Cortese A, Vita G, Luigetti M, Russo M, Bisogni G, Sabatelli M, Manganelli F, Santoro L, Cavallaro T, Fabrizi GM, Schenone A, Grandis M, Gemelli C, Mauro A, Pradotto LG, Gentile L, Stancanelli C, Lozza A, Perlini S, Piscosquito G, Calabrese D, Mazzeo A, Obici L, Pareyson D.J Neurol. 2016 May;263(5):925-926. No abstract available. PMID: 27098978
10:Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area. Cortese A, Vita G, Luigetti M, Russo M, Bisogni G, Sabatelli M, Manganelli F, Santoro L, Cavallaro T, Fabrizi GM, Schenone A, Grandis M, Gemelli C, Mauro A, Pradotto LG, Gentile L, Stancanelli C, Lozza A, Perlini S, Piscosquito G, Calabrese D, Mazzeo A, Obici L, Pareyson D.J Neurol. 2016 May;263(5):916-24. doi: 10.1007/s00415-016-8064-9. Epub 2016 Mar 16. Erratum in: J Neurol. 2016 May;263(5):925-6. PMID: 26984605