Bruton tyrosine kinase (Btk) is a member of the Tec family kinases with a well-characterized role in B-cell antigen receptor (BCR)-signaling and B-cell activation. Btk plays a crucial role in B cell development and activation through the BCR signaling pathway. And it represents a new target for diseases characterized by inappropriate B cell activity. Bruton tyrosine kinase is a kinase expressed exclusively in B cells and myeloid cells. Btk plays an essential role in the BCR signaling pathway.
JDB175 is an Orally Active BTK Inhibitor for Central Nervous System Lymphoma Research
JDB175 is a highly selective BTK inhibitor with oral activity and excellent blood-brain barrier penetration. And it shows good activity in the mouse model of central nervous system lymphoma without obvious signs of toxicity. Moreover, it effectively inhibits the proliferation of BTK signaling pathway of human lymphoma cells, induces cell cycle arrest, and promotes cell apoptosis .
In Vitro, JDB175 (15-40 μM, 48 h) can effectively inhibit the phosphorylation of BTK in Namalwa and Raji cells, down-regulate the expression of cyclin D1 and CDK2, and up-regulate the expression of P21. JDB175 (15 μM, 48 h) significantly increases the G0/G1 phase distribution in Namalwa, SU-DHL-4, Raji and Ramos cells. JDB175 (20-40 μM, 72 h) shows strong apoptosis-inducing effect in Namalwa, SU-DHL-4, Raji and Ramos cells.
In Vivo, JDB175 (10 mg/kg, oral gavage, 0.5 h) has strong potential to penetrate the blood-brain barrier in rats. And it has shown good ability to inhibit central nervous system lymphoma. JDB175 (150 mg/kg, oral gavage, 3 days) shows effective inhibitory effect and good safety in nude mouse lymphoma tumor model.
In conclusion, JDB175 is an orally active BTK inhibitor for central nervous system lymphoma research.