Pyridoclax (MR29072)

Description: Pyridoclax, formerly known as MR29072, is a potent and selective Mcl-1 inhibitor. Without cytotoxic activity when administered as a single agent, pyridoclax induced apoptosis in combination with Bcl-xL-targeting siRNA or with ABT-737 in ovarian, lung, and mesothelioma cancer cells. Bcl-xL and Mcl-1 cooperate to protect cancer cells against apoptosis and their concomitant inhibition leads to massive apoptosis even in the absence of chemotherapy. Whereas Bcl-xL inhibitors are now available, Mcl-1 inhibition, required to sensitize cells to Bcl-xL-targeting strategies, remains problematic.

References: Gloaguen C, Voisin-Chiret AS, Sopkova-de Oliveira Santos J, Fogha J, Gautier F, De Giorgi M, Burzicki G, Perato S, PÃtigny-Lechartier C, Simonin-Le Jeune K, Brotin E, Goux D, N'Diaye M, Lambert B, Louis MH, Ligat L, Lopez F, Juin P, Bureau R, Rault S, Poulain L. First Evidence That Oligopyridines, alpha-Helix Foldamers, Inhibit Mcl-1 and Sensitize Ovarian Carcinoma Cells to Bcl-xL-Targeting Strategies. J Med Chem. 2015 Feb 26; 58(4):1644-68. doi: 10.1021/jm500672y. Epub 2015 Feb 4. PubMed PMID: 25585174.