GNE-431 is a potent, selective and noncovalent “pan- BTK ” inhibitor against C481R, T474I and T474Ms mutants. GNE-431 shows potency against wild-type BTK ( IC 50 = 3.2 nM) andpotency against C481S mutant ( IC 50 = 2.5 nM). GNE-431 is proming for rasearch of haematological disorders and autoimmune diseases.