Acoramidis hydrochloride (Alxn2060 hydrochloride) is an orally active and selective kinetic stabilizer of WT and V122I- TTR (transthyretin) . Acoramidis hydrochloride is used in the study for transthyretin amyloidosis.

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 [1] . Acoramidis (AG10) stimulates the mitochondrial QO2 in a concentration-dependent manner between 10 and 100 μM [3] . 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) [1] . Western Blot Analysis [1] . 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 an animal model using Wistar rats [1], AG10 was administered orally via gavage at a dosage of 50 mg/kg/d for toxicity analysis over a 28-day period. Subsequent results indicated a plasma C max of approximately 40 μM. Histopathological evaluations of the liver, kidney, heart, spleen, thymus, and lung revealed no signs of pathological processes in the AG10-treated subjects.