CB6644

CB6644 is a potent and selective small molecule inhibitor of the RUVBL1/RUVBL2 (also known as Pontin/Reptin) AAA+ ATPase complex. RUVBL1 and RUVBL2 are highly conserved proteins that function as molecular chaperones and are integral components of various multi-protein complexes involved in chromatin remodeling, transcriptional regulation, and DNA damage repair. In oncogenic contexts, the RUVBL1/2 complex is often overexpressed and facilitates tumor progression by modulating key signaling pathways. CB6644 works by inhibiting the ATPase activity of the complex, which leads to the suppression of mTORC1 signaling, reduction of PD-L1 expression, and disruption of YTHDF1-mediated oncogenic translation. Preclinical studies have demonstrated that CB6644 can arrest cell proliferation, induce apoptosis, and enhance immune cell infiltration in models of oral squamous cell carcinoma and colorectal cancer.