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NAMPT inhibitors and activators act on nicotinamide phosphoribosyltransferase in the NAD+ salvage pathway. NAMPT converts nicotinamide to nicotinamide mononucleotide, the rate-limiting step in recycling nicotinamide adenine dinucleotide (NAD+). A 2004 study showed that this salvage pathway sustains NAD+ levels and regulates sirtuin deacetylase activity in mammalian cells. FK866, described in 2003 as a noncompetitive NAMPT inhibitor, depletes NAD+ and triggers apoptosis in tumor cell lines. CHS-828, GNE-617 and STF 118804 are further inhibitors, and KPT 9274 inhibits both NAMPT and p21-activated kinase 4 (PAK4). P7C3, P7C3-A20 and SBI-797812 act in the opposite direction, and P7C3 compounds were shown in 2014 to activate NAMPT in studies of neuroprotection.
