Acoramidis (AG10) hydrochloride is an orally active and selective kinetic stabilizer of WT and V122I- TTR (transthyretin). Acoramidis (AG10) hydrochloride is used in the study for transthyretin amyloidosis.
In Vitro
Acoramidis (AG10, 0.1-10 μM for TTR ∼5 µM) stabilizes V122I- and WT-TTR equally well and also exceeds their efficacy to stabilize WT and mutant TTR in whole serum. Acoramidis (AG10) stimulates the mitochondrial QO2 in a concentration-dependent manner between 10 and 100 μM. Acoramidis (AG10) has very minimal inhibition of two common off-targets in drug discovery, the potassium ion channel hERG (IC 50 > 100 µM) and a number of cytochrome P450 isozymes (IC 50 > 50 µM) (low toxicity). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot Analysis. Cell Line: Human serum (TTR ∼5 µM). Concentration: 0.1 and 10 μM. Incubation Time: 72 h. Result: Was significantly more effective than tafamidis in stabilizing TTR. The concentration of AG10 to 10 µM resulted in stabilization of almost all of TTR in serum.
In Vivo
Animal Model: Wistar rats . Dosage: 50 mg/kg/d (Toxicity Analysis). Administration: Oral gavage, daily for 28 d. Result: Showed the plasma C max of ∼40 µM and histopathological evaluation of liver, kidney, heart, spleen, thymus, and lung showed no signs of pathologic processes in the AG10-treated animals
