CC-885 is a modulator of cereblon (CRBN). It has potent anti-tumour activity.

CC-885 exhibits stronger antiproliferative effects than Lenalidomide and Pomalidomide across various cell types, including acute myeloblastic leukemia (AML) cell lines, THLE-2 human liver epithelial cells, and human peripheral blood mononuclear cells (PBMC), with IC50 values ranging from 10×-6-1 μM. The compound's efficacy was also assessed in 293T HEK cells engineered to express variants of GSPT1 that are either sensitive or resistant to CC-885. The study further explores the mechanism behind CC-885's cytotoxicity, particularly its dependency on cereblon-mediated degradation of GSPT1. By utilizing a GSPT1 mutant which maintains its functionality but lacks the cereblon binding affected by CC-885, the research distinguishes GSPT1's role from other potential targets. Notably, cells overexpressing the CC-885-resistant GSPT1 variant (GSPT1Δ(1–138)/(G575N)) were completely resistant to the compound's inhibitory effects on cell proliferation. In contrast, overexpressing a CC-885-sensitive variant (GSPT1Δ(1-138)) provided only partial protection against these effects, indicating the critical role of GSPT1 degradation in CC-885's mechanism of action. Similar outcomes were observed in AML cell lines[1].