molecules of the month

The GlaxoSmithKline (GSK) Z α1-antitrypsin stabilizer (“compound 13,” GSK716) acts by blocking the formation of polymers within the endoplasmic reticulum of hepatocytes for treatment of α1-antitrypsin deficiency. It was identified through a DNA-encoded library screen with a nominal diversity of 2 trillion components. Compound 13 showed an excellent selectivity profile toward α1-antitrypsin. The 1 mg/kg i.v. infusion of compound 13 demonstrated moderate bioavailability in rat and was predicted to have high oral bioavailability in human. This molecule is interesting as the starting point came from a DEL screen and has a rare corrector mechanism of action.