SBI-797812 functions as an orally active activator of nicotinamide phosphoribosyltransferase (NAMPT). It induces a shift in NAMPT activity towards NMN formation, enhances NAMPT's affinity for ATP, stabilizes phosphorylated NAMPT, facilitates the consumption of pyrophosphate by-product, and attenuates feedback inhibition by NAD+. SBI-797812 leads to elevated intracellular nicotinamide mononucleotide (NMN) levels and increased liver NAD+ concentrations in mice[1][2].
体内研究
SBI-797812 (10 mg/kg; i.p. or o.p.; single dose) exhibits substantial plasma exposure following intraperitoneal administration, with Cmax value of 3297 ng/mL, 8.2 μM[1].
SBI-797812 (20 mg/kg; i.p.; single dose; measured 2 h post-dose) markedly elevates NAD+ levels in mouse liver[1].
体外研究
SBI-797812 (0-4 μM; 4 h) dose-dependently stimulates NAMPT activation, exhibiting an EC50 value of 0.37 μM, and (1 μM, 2 μM; 1 h) enhances NAMPT-mediated NMN production in cells[1].
SBI-797812 (2 μM; 1 or 4 h) induces activation of NAMPT (30 nM), dependent on ATP (2 mM) availability[1].
SBI-797812 (5 μM; 2 h) influences PP (20 μM) utilization and the reactivity of pHisNAMPT[1].
SBI-797812 (0.4, 2, 10 μM; 4 h) elevates the concentration of nicotinamide mononucleotide (NMN) and NAD+ in A549 human lung carcinoma cells, as well as in human or mouse primary myotubes at 10 μM[1].
SBI-797812, functioning as an NRAMPT activator, contributes to the progression of aging. NAMPT serves as a rate-limiting enzyme in the NAD+ salvage pathway of the aging/senescence process[2].
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