CB-6644 (CB6644) is a potent, selective, allosteric, orally bioavailable inhibitor of the ATPase activity of RUVBL1/2 complex with IC50 of 15 nM.
CB-6644 displays no appreciable activity against a panel of related AAA ATPases in ATPase assays (IC50>100 uM), including the p97.
CB-6644 binds to the RUVBL1/2 complex in an ATP-dependent manner.
CB-6644 interacts with the RUVBL1/2 complex in cells and induces cancer cell death in a panel of 123 cancer cell lines (EC50=41-785 nM), dose-dependently accumulates both p53 and p21 with EC50 of 0.24 and 0.15 uM in HCT116 cells.
CB-6644 demonstrates antitumor activity in xenograft tumor models.
