BTK inhibitor 18

BTK inhibitor 18 is a potent, selective,orally active and covalent Btk inhibitor with a IC50 of 142 nM. BTK inhibitor 18 has anti-inflammatory activities[1].

BTK inhibitor 18 (Compound 27) irreversibly inhibits BTK by targeting a noncatalytic cysteine residue (Cys481) for covalent bond formation[1].BTK inhibitor 18 (Compound 27) inhibits anti-IgM-induced activation of B cells in human whole blood with an IC50 of 84 nM[1]. BTK inhibitor 18 (Compound 27) also inhibits BMX, LCK, ErbB4, TEC, and TXK kinases with IC50 values of 129 nM, 130 nM, 377 nM, 409 nM, 1770 nM, respectively[1].

BTK inhibitor 18 (Compound 27; 1-30 mg/kg; oral administration; once a day; for 7 days) treatment shows dose-dependent efficacy at reducing joint inflammation in a rat collagen-induced arthritis model[1].The IV and PO pharmacokinetics of BTK inhibitor 18 (Compound 27) are investigated in nonfasted rats (1 and 5 mg/kg IV and PO) and fasted dogs (0.5 and 2.5 mg/kg IV and PO). IV pharmacokinetics are characterized by moderate clearance in rat and low clearance in dog, a moderate volume of distribution, and a short plasma half-life across both species (T1/2 of 0.3 h and 1.9 h for rat and dog, respectively). The oral bioavailability is 30% and 68% in rat and dog, respectively[1].

[1]. Mark S Tichenor, et al. Discovery of a Potent and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase with Oral Anti-Inflammatory Activity. ACS Med Chem Lett. 2021 Apr 5;12(5):782-790.