Research Progress and Clinical Application Potential of Novel Small Molecule Inhibitors Targeting Apoptosis
SHI Shan1, QIU Miaozhen1*, YANG Dajun1,2*
Apoptosis represents a form of programmed cell death, integral to the physiological processes by which multicellular organisms eliminate damaged or surplus cells. This highly regulated phenomenon is frequently disrupted, correlating strongly with various pathological conditions, including malignancies, autoimmune disorders, and neuroinflammatory diseases. A hallmark of cancer is the resistance to apoptosis, which often stems from a complex dysregulation between intrinsic and extrinsic survival signals and pro-apoptotic factors. The balance between pro-apoptotic and anti-apoptotic signals, primarily mediated by members of the Bcl-2 protein family, ultimately dictates cellular fate. Over the years, considerable effort has been devoted to the identification and development of pharmacological agents aimed at inducing apoptosis in neoplastic cells to inhibit tumor progression. Particularly, small molecule inhibitors targeting the Bcl-2 family, IAPs (inhibitors of apoptosis proteins), and the MDM2-p53 signaling pathway have demonstrated substantial clinical potential in facilitating tumor cell apoptosis. This review seeks to systematically elucidate the fundamental structures and physiological roles of these critical targets, assess the efficacy and limitations of early-stage inhibitors, and provide a comprehensive overview of the advancements and future applications of novel small molecule inhibitors developed by Ascentage Pharma research team, specifically designed to enhance apoptotic pathways in oncological therapy.
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