抗癌新希望：强效Smac模拟物SM-1200引发持久肿瘤消退，极具临床潜力！本研究中PK实验通过美迪西进行

SM-1200, a potent bivalent Smac mimetic, induces rapid, complete, and durable tumor regression in mice. X-linked inhibitor of apoptosis protein (XIAP) and cellular IAP1/2 (cIAP1/2) regulate apoptosis and are promising cancer therapeutic targets. Smac (second mitochondria-derived activator of caspases), also known as DIABLO, antagonizes IAP proteins. Researchers designed and synthesized new compounds based on bivalent Smac mimetics, leading to the identification of SM-1200 (compound 12).

SM-1200 binds to XIAP (K_i=0.5 nM), cIAP1 (K_i=3.7 nM), and cIAP2 (K_i=5.4 nM), and inhibits growth of MDA-MB-231 breast cancer (IC₅₀=11.0 nM) and SK-OV-3 ovarian cancer (IC₅₀=28.2 nM) cell lines. With an improved pharmacokinetic profile compared to previous bivalent Smac mimetics, SM-1200 effectively induces rapid and durable tumor regression in the MDA-MB-231 xenograft model. These findings suggest SM-1200 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development.

Pharmacokinetic studies in rats

Pharmacokinetic (PK) studies of bivalent Smac mimetics were performed in male Sprague Dawley rats (body weight: 250–270 g) by Medicilon. Before the pharmacokinetic studies, animals were carotid cannulated.

Reference:

Rong Sheng, et al. A potent bivalent Smac mimetic (SM-1200) achieving rapid, complete, and durable tumor regression in mice. J Med Chem. 2013 May 23;56(10):3969-79. doi: 10.1021/jm400216d.