CB-5083 + dexamethasone

**CB-5083 + dexamethasone** is a combination of a first-in-class inhibitor of **valosin-containing protein (VCP, also known as p97)**, CB-5083, with dexamethasone, a synthetic glucocorticoid corticosteroid, investigated as a potential therapy for relapsed/refractory multiple myeloma (RRMM). CB-5083 acts by inhibiting p97/VCP, disrupting protein homeostasis, leading to accumulation of polyubiquitinated proteins, induction of the unfolded protein response (UPR), and apoptotic cell death in cancer cells[1][2][4][5]. Dexamethasone provides anti-inflammatory and cytotoxic effects and is commonly used to enhance the efficacy of anticancer regimens. CB-5083, originally developed by Cleave Biosciences, underwent phase I clinical trials in combination with dexamethasone, but development was terminated due to off-target visual adverse events related to phosphodiesterase-6 inhibition[1][4][5]. In preclinical and early clinical settings, CB-5083 showed promising synergy with proteasome inhibitors and activity in VCP-driven neuromuscular diseases, but sustained development as a cancer therapeutic was not achieved[1][5].