BTM-3528

BTM-3528 is an orally bioavailable small molecule pyrazolo-thiazole derivative developed by Bantam Pharmaceutical that targets mitochondrial dynamics and homeostasis. It acts as an activator of the mitochondrial protease OMA1. Activation of OMA1 triggers the cleavage of DELE1 and OPA1, leading to mitochondrial fragmentation and the hyperactivation of the integrated stress response (ISR) via the ATF4 pathway. This mechanism results in cell growth arrest and apoptosis. BTM-3528 has shown preclinical anti-proliferative activity in various hematological malignancies, particularly aggressive B-cell lymphomas like diffuse large B-cell lymphoma (DLBCL), as well as several solid tumor models. It is mechanistically distinct from mitochondrial electron transport inhibitors.