产品描述:
NX-2127 is a proteolysis-targeting chimera (PROTAC) containing a binding moiety for Bruton's tyrosine kinase (BTK) linked to a cereblon (CRBN) binding moiety.{72361} It induces degradation of wild-type BTK (DC50 = 1.9 nM) and BTK mutants containing drug resistance-conferring mutations, including BTKC481S, BTKV416L, BTKT474I, and BTKL528W in TMD8 diffuse large B cell lymphoma (DLBCL) cells (DC50s = 9.7, 4.2, 2.4, and 1.9 nM, respectively).{72362} NX-2127 also degrades the lymphocyte transcription factors Ikaros family zinc finger protein 1 (IKZF1) and IKZF3 (DC50s = 57 and 36 nM, respectively) and induces T cell activation in primary human T cells stimulated by anti-CD3 and anti-CD28 antibodies.{72361} It reduces BTK levels in circulating mouse B cells to 12% of baseline when administered at a dose of 30 mg/kg. NX-2127 (10, 30, and 90 mg/kg per day) induces intratumoral BTK, IKZF1, and IKZF3 degradation in a TMD8 mouse xenograft model. It also reduces tumor growth in mouse xenograft models using TMD8 cells expressing wild-type BTK or BTKC481S.