About CB-5339 (VCP/p97 inhibitor)
CB-5339, an oral second-generation, small molecule VCP/p97 inhibitor, is being evaluated by our partner Cleave Therapeutics in a Phase 1 clinical trial in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
VCP/p97 inhibitors exploit molecular features that define cancer cell growth and metabolism. VCP/p97 plays a critical role in protein homeostasis processes such as endoplasmic reticulum associated degradation (ERAD) and chromatin-associated degradation (CAD), as well as the DNA damage response (DDR). These key cellular stress pathways are known to represent sensitivities critical to cancer cell survival. Cellular stress provides an attractive means of targeting non-oncogene addiction as a way to combat tumor heterogeneity and emerging resistance to targeted therapies. Such an approach has the added benefit of broad applicability, not dependent on a single driver mutation and potential efficacy across cancer types.