| Description | Tafamidis (Fx-1006A) is a kinetic stabilizer of transthyretin (TTR) that prevents amyloidogenesis by wild-type and mutant TTRs. It binds to TTR with negative cooperativity (Kd1: 3 nM; Kd2: 278 nM) to stabilize the TTR dimer-dimer interface and inhibit tetrameric dissociation. Tafamidis stabilizes wild-type and clinically significant V30M and V122I mutant TTR amyloidogenic homotetramers (EC50s: 2.7-3.2 μM) under fibril-promoting, denaturing, and physiological conditions in vitro. It stabilizes TTR heterotetramers containing wild-type and mutant subunits ex vivo in human plasma derived from patients carrying V30M or V1221 mutations when used at a concentration of 7.2 μM. Formulations containing tafamidis have been used for the treatment of familial amyloid polyneuropathy. |
| Target activity | TTR (WT, V30M, V122I):2.7-3.2 μM(ec50) |
| Synonyms | 他发米帝司甲葡胺, 氯苯唑酸, Fx-1006A |
| molecular weight | 308.12 |
| Molecular formula | C14H7Cl2NO3 |
| CAS | 594839-88-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 2 mg/mL DMSO: 10 mg/mL (32.45 mM) |
| References | 1. Bulawa, C.E., et al., Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci U S A, 2012. 109(24): p. 9629-34. 2. Scott L J. Tafamidis: A Review of Its Use in Familial Amyloid Polyneuropathy[J]. Drugs, 2014, 74(12):1371. |