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: 0.09 nM (NMPRTase)

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Cea M, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 2012 Oct 25;120(17):3519-29.  [Content Brief]

  [2]. Magnone M, et al. NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes. J Biol Chem. 2012 Jun 15;287(25):21067-81.  [Content Brief]

  [3]. Thakur BK, et al. Inhibition of NAMPT pathway by FK866 activates the function of p53 in HEK293T cells. Biochem Biophys Res Commun. 2012 Aug 3;424(3):371-7.  [Content Brief]

  [4]. Hasmann M, Schemainda I. FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 2003 Nov 1;63(21):7436-42.  [Content Brief]