APG-115 + APG-2575

**APG-115 + APG-2575** is a rationally designed combination therapy of two small molecule targeted agents developed for hematologic malignancies and solid tumors. APG-115 is a selective oral inhibitor of MDM2, designed to activate p53 tumor suppressor function by blocking the MDM2-p53 interaction, thereby inducing cell cycle arrest and apoptosis in cancer cells. APG-2575 is an oral selective inhibitor of Bcl-2, restoring apoptosis in cancer cells by disabling anti-apoptotic Bcl-2, triggering mitochondrial outer-membrane permeabilization, release of cytochrome c, and caspase activation. The combination aims for *synthetic lethality* by simultaneously inhibiting the MDM2-TP53 and BCL-2 pathways, leading to potentiated antitumor activity, especially in diseases with wild-type p53 and Bcl-2 overexpression. Preclinical studies demonstrated synergistic cell killing and tumor regression, and the combination is in clinical development for relapsed or refractory T-cell prolymphocytic leukemia (T-PLL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL)[1][2][4].

Other names

alrizomadlin + lisaftoclax