Information
CC-92480 CC-92480 is a novel protein degrader and a cereblon E3 ligase modulator (CELMoD) that has anti-myeloma activity.
Targets
Cereblon
In vitro
CC-92480 has a unique and rapid degradation profile: the enhanced efficiency to drive the formation of the protein−protein interaction between Aiolos and cereblon, inducing targeted docking to the CRL4-CRBN E3 ubiquitin ligase complex. The CC-92480-dependent binding of Aiolos/Ikaros to CRBN leads to polyubiquitination and ultimately proteasome-mediated degradation of protein. Rapid and extensive loss of Aiolos/Ikaros in sensitive cells, such as multiple myeloma cells, results in apoptosis and subsequent cell death.
In vivo
CC-92480 is evaluated in efficacy models to assess tumor growth inhibition in tumor bearing mice. When tumors reaches approximately 150 mm3, mice are randomized and treated once daily (q.d.) orally with vehicle control or various dosage strengths of CC-92480. Both the 3 and 10 mg/kg doses give near maximal response in this model, while the lowest dose tested (1 mg/kg) shows 75% reduction in tumor volume by the end of the study.
Cell Research(from reference)
Cell lines：H929 R10-1 cells
Concentrations：1 nM, 10 nM, 100 nM
Incubation Time：4 h, 72 h
I2616062