Small molecule inhibitors of NAMPT
Novel inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) can treat cancer, and also has potential in other NAMPT-related conditions like Alzheimer’s disease, diabetes and arthritis. NAMPT, the first and rate limiting enzyme of the mammalian NAD+ recycling pathway, is currently being tested by others as a target through several Phase I and Phase I/II clinical trials against multiple forms of cancer. In the present invention, a new class of NAMPT inhibitors has been developed. The concentration dependent activities of these agents have been tested in-vitro and directly compared against six human tumor cell lines including: breast, colon, glioma, prostate, pancreatic, and lung cancer. Several of these agents demonstrate significantly higher activity than other known NAMPT inhibitors in vitro, exhibiting significantly lower IC50 values, as well as higher cancer cell anti-proliferative effects.