DT204 (DT-204) is a novel SCFSkp2 inhibitor that reduces Skp2 binding to Cullin-1 and Commd1, synergistically enhances BTZ-induced apoptosis.
DT204 stablizes and increases p27 levels, does not increase the level of p53, demonstrates potential synergy with CI values of 0.7, 0.8 and 0.7 for RPMI8226, U266 and MM1.S respectively combined with 1 nM BTZ, co-treatment induces apoptosis in cells resistant to the proteasome inhibitors BTZ, carfilzomib or ixazomib.
DT204 overcomes drug resistance and reduces the in vivo growth of myeloma tumors in murine models.
