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。
体外研究
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.
体内研究
CB-5083 (75 mg/kg; oral administration; qd; for 2 weeks) shows antitumor activity in an HCT 116 tumor xenograft model.
CB-5083 exhibits terminal elimination half-life (T1/2=2.56 h), moderate oral bioavailability (mouse 41%) and Cmax (mouse 7.95 μM) following oral administration (25 mg/kg) in female nude mice.
CB-5083 exhibits terminal elimination half-life (T1/2=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.
CB-5083 has good metabolic stability with a 102 min T1/2 in a mouse liver microsomal stability study and a 172 min T1/2 in a hepatocyte stability study.
Animal Model:
Nu/Nu nude female mice bearing established human tumor xenografts derived from HCT 116 colon
Dosage:
75 mg/kg
Administration:
Administered orally using every day (qd) dosing, for 2 weeks.
Result:
Showed more profound antitumor activity.
分子式
C24H23N5O2
分子量
413.47
CAS号
1542705-92-9
运输条件
Room temperature in continental US; may vary elsewhere.