Poseltinib is an orally active, selective, and irreversible inhibitor of Bruton's tyrosine kinase (BTK), with an IC50 value of 1.95 nM. Poseltinib demonstrates 0.3-, 2.3-, and 2.4-fold higher selectivity for BTK over BMX, TEC, and TXK, respectively. Poseltinib covalently binds to cysteine 481 in BTK’s active site, thereby inhibiting BCR-, FcR-, and TLR-mediated signaling pathways.

BTK:1.95 nM

Methods: Ramos B lymphoma cells of Homo sapiens were treated with Poseltinib (0.1-100 nM, 30 min), and the expression of related proteins was analyzed by Western Blot.
Results: Poseltinib simultaneously blocked the autophosphorylation of BTK and the phosphorylation of its physiological substrate PLCγ2, with IC50 values both less than 10 nM. [1]

Methods: Poseltinib (3-30 mg/kg, daily) was orally administered to MRL/lpr and NZB/W F1 mouse models to evaluate the therapeutic effects of Poseltinib on systemic lupus erythematosus (SLE)-like disease characteristics in mice.
Results: By inhibiting BTK, Poseltinib effectively reduced the overactivation of B cells and the production of autoantibodies, significantly alleviating the progression of SLE and lupus nephritis (LN) in mice. Poseltinib demonstrated notable improvements in skin lesions, renal function, kidney injury, and inflammation, while also increasing survival rates. [1]