1492903-45-3Relevant academic research and scientific papers
Novel dimeric Smac analogs as prospective anticancer agents
Micewicz, Ewa D.,Luong, Hai T.,Jung, Chun-Ling,Waring, Alan J.,McBride, William H.,Ruchala, Piotr
, p. 1452 - 1457 (2014)
A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)-4-Benzyl-Pro-Xaa-cysteamide, was synthesized (Xaa = hydrophobic residue). The library was screened in vitro against human breast cancer cell lines MCF-7 and MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X was tested in vivo and in physiological conditions (mouse model) it exerted a potent anticancer effect resulting in ～23.4 days of tumor growth delay at 7.5 mg/kg dose. Collectively, our findings suggest that bivalent Smac analogs obtained via S-alkylation protocol may be a suitable platform for the development of new anticancer therapeutics.
