CB-5083 recently began Phase 1 testing in relapsed/refractory or refractory multiple myeloma, and advanced solid tumors (see clinicaltrials.gov for more information). CB-5083 is a potent, highly selective, oral p97 inhibitor with broad in vivo activity in both multiple myeloma and solid tumor xenografts. CB-5083 is a potent inhibitor of endoplasmic reticulum associated degradation and induces a lethal unfodled protein response. Multiple myeloma is a cancer with a well-known dependence on protein homeostasis for survival with the proteasome inhibitors bortezomib and carfilzomib as FDA approved drugs. These agents are not effective in solid tumors owing to both chemistry and pharmacology limitations. Not only has Cleave demonstrated activity in solid tumors with CB-5083, we have also identified molecular features that correlate to increased anti-tumor activity in preclinical models.
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