| Description | AG-10 (Acoramidis) is an orally active and selective kinetic stabilizer of TTR (transthyretin). AG-10 exhibits activity for WT and V122I-TTR. AG-10 is used in the study of transthyretin amyloidosis. |
| In vitro | AG-10 (0.1-10 μM for TTR ∼5 µM) stabilizes WT- and V122I-TTR equally well and also exceeds their efficacy to stabilize WT and mutant TTR in whole serum. AG-10 exhibits minimal inhibition of two common off-targets in drug discovery, the potassium ion channel hERG (IC50 > 100 µM) and a number of cytochrome P450 isozymes (IC50 > 50 µM) (low toxicity)[1]. AG-10 (10-100 μM) stimulates the mitochondrial QO2 in a concentration-dependent manner[2]. |
| In vivo | AG-10 (Oral gavage; 50 mg/kg/d; daily for 28 d) exhibited the plasma Cmax of ∼40 µM and histopathological evaluation of liver, thymus, kidney, spleen, heart, and lung showed no signs of pathologic processes in the AG10-treated Wistar rats[1]. |
| Synonyms | Acoramidis |
| molecular weight | 292.31 |
| Molecular formula | C15H17FN2O3 |
| CAS | 1446711-81-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 4.8 mg/mL (16.42 mM) |
| References | 1. Sravan C Penchala, et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9992-7. 2. Stephen P Soltoff, et al. Evidence that tyrphostins AG10 and AG18 are mitochondrial uncouplers that alter phosphorylation-dependent cell signaling. J Biol Chem. 2004 Mar 19;279(12):10910-8. 3. Jonathan C Fox, et al. First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2020 Jan;9(1):115-129. |