CB-5083

CB-5083 is a first-in-class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase/VCP. CB-5083 selectively inhibits p97 through its D2 site with the IC₅₀ of 11 nM^[1]. IC50 & Target:IC50: 11 nM (p97)^[1] In Vitro: CB-5083 shows cell killing potency with IC₅₀s of 0.68, 0.68, 1.03, and 0.49 μM for lung carcinoma A549 CTG, A549 K48, A549 CHOP, and A549 p62, respectively^[1]. In Vivo: CB-5083 (75 mg/kg; oral administration; qd; for 2 weeks) shows antitumor activity in an HCT 116 tumor xenograft model^[1].
CB-5083 exhibits terminal elimination half-life (T_1/2=2.56 h), moderate oral bioavailability (mouse 41%) and C_max (mouse 7.95 μM) following oral administration (25 mg/kg) in female nude mice^[1].
CB-5083 exhibits terminal elimination half-life (T_1/2=2.83 h) due to high plasma clearance (5.9 mL/min/kg respectively) combined with large volumes of distribution (418 mL/kg respectively) following intravenous administration (3.0 mg/kg) in female nude mice^[1].
CB-5083 has good metabolic stability with a 102 min T_1/2 in a mouse liver microsomal stability study and a 172 min T_1/2 in a hepatocyte stability study^[1].