tcsc1055 (E) -Daporinad

FK866 is an effective inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase) with an IC₅₀ of 0.09 nM.

IC50 & Target: IC50: 0.09 nM (NMPRTase)

In Vitro: Nampt inhibition with FK866 induces significant NAD⁺ intracellular reduction and selectively kills MM cells. FK866-induced cell death is associated with inhibition of Nampt activity, rather than protein expression, and higher NAD⁺ baseline levels in MM cells than normal PBMCs confer FK866 sensitivity. FK866 abrogates the survival advantage conferred by the bone marrow microenvironment^[1]. FK866 prevents the [Ca²⁺]i increase induced by different mitogens and reduces the Ca²⁺ content of TG-responsive Ca²⁺ stores in Jurkat and in activated PBLs. FK866 reduces the Ca²⁺ content of TG-responsive Ca²⁺ stores in Jurkat cells but not in Bcl2-Jurkat cells^[2]. Inhibition of NAMPT by FK866, or inhibition of SIRT by nicotinamide decreases proliferation and triggered death of 293T cells involving the p53 acetylation pathway^[3].

In Vivo: FK866 (30 mg/kg, i.p.) decreases the tumor burden in CB17-SCID mice, and the tumor tissue demonstrates a significant decrease in ERK phosphorylation and proteolytic cleavage of LC3^[1].