CC-885

1010100-07-8

C22H21ClN4O4

DMSO : 67.5 mg/mL (153.10 mM; Need ultrasonic)

PROTAC

CC-885 is a cereblon (CRBN) modulator with potent anti-tumour activity. IC50 & Target: CRBN^[1]. In Vitro: Acute myeloblatlic leukemia (AML) cell lines, human liver epithelial cell line (THLE-2) and human peripheral blood mononuclear cells (PBMC) are treated with varying concentrations of CC-885, with IC₅₀s of 10x^-6-1 uM. The effect of CC-885 on cell proliferation in AML cell lines, THLE-2 and human PBMC is more powerful than Lenalidomide and Pomalidomide with IC₅₀s>10 uM. To address whether the cereblon-dependent degradation of GSPT1 is responsible for the cytotoxic effects of CC-885, a GSPT1 mutant that retains its normal function, but loses CC-885-dependent cereblon binding, is used to distinguish the role of GSPT1 from that of other substrates. CC-885 is tested in 293T HEK cells stably expressing the CC-885-sensitive or -resistant GSPT1 variants. Overexpression of a resistant variant GSPT1delta(1�138)/(G575N) completely abrogate the CC-885-induced anti-proliferation, whereas overexpression of a CC-885-sensitive variant GSPT1delta(1-138) only confer partial protection. Similar results are obtained in AML cell lines^[1].