Daporinad

Daporinad (FK866) is a non-competitive inhibitor of nicotinamide phosphoribosyltransferase (Nampt), with a K_i value of 0.3 nM. Daporinad depletes NAD+ and ATP levels, inhibits mTORC1 and MAPK/ERK pathways, and activates TFEB to induce autophagy. Daporinad causes the depletion of the endoplasmic reticulum Ca²⁺ pool, ultimately weakening the mitogen-induced Ca²⁺ signal and the activation and function of T cells. Daporinad induces cell cycle arrest and apoptosis, and inhibits cell proliferation. Daporinad can be used for the study of myeloma, liver cancer, and immunosuppression^[1][2][3][4]. IC50 & Target:IC50: 0.09 nM (NMPRTase) In Vitro:Nampt inhibition with (E)-Daporinad (FK866) induces significant NAD⁺ intracellular reduction and selectively kills MM cells. (E)-Daporinad (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 (E)-Daporinad (FK866) sensitivity. (E)-Daporinad (FK866) abrogates the survival advantage conferred by the bone marrow microenvironment^[1]. (E)-Daporinad (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. (E)-Daporinad (FK866) reduces the Ca²⁺ content of TG-responsive Ca²⁺ stores in Jurkat cells but not in Bcl2-Jurkat cells^[2]. Inhibition of NAMPT by (E)-Daporinad (FK866), or inhibition of SIRT by nicotinamide decreases proliferation and triggered death of 293T cells involving the p53 acetylation pathway^[3]. In Vivo:Daporinad (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].