CP5V

CP5V is a proteolysis-targeting chimera (PROTAC) designed to selectively degrade cell division cycle protein 20 (CDC20). CDC20 is a key regulator of the cell cycle that is overexpressed in the lungs and pulmonary artery (PA) cells of patients with pulmonary arterial hypertension (PAH). Unlike canonical CDC20 signaling which acts via the APC/C E3 ubiquitin ligase, CP5V targets a non-canonical pathway where CDC20 overexpression leads to the accumulation of the pro-proliferative protein securin and the depletion of the pro-apoptotic protein BIM. By degrading CDC20, CP5V reduces securin levels and restores BIM, thereby inhibiting the hyper-proliferation and apoptosis resistance of PA smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs). In preclinical models, CP5V has demonstrated the ability to reverse established pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy.