SBI-797812 is an orally active nicotinamide phosphoribosyltransferase (NAMPT) activator. SBI-797812 shifts NAMPT to NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD+. SBI-797812 increases intracellular nicotinamide mononucleotide (NMN) and elevates liver NAD+ in mice[2].IC50 & Target: NAMPTIn Vitro: SBI-797812 (0-4 μM; 4 h) activates NAMPT in a dose-dependent manner with an EC50 value of 0.37 μM, and (1 μM, 2 μM; 1 h) increases NAMPT-mediated NMN in cells.
SBI-797812 (2 μM; 1 or 4 h) exerts NAMPT (30 nM) activation requiring ATP (2 mM).
SBI-797812 (5 μM; 2 h) impacts PP (20 μM) consumption and pHisNAMPT reactivity.
SBI-797812 (0.4, 2, 10 μM; 4 h) increases the level of nicotinamide mononucleotide (NMN) and NAD+ in A549 human lung carcinoma cells as well as in human or mouse primary myotubes at 10 μM.
SBI-797812, as an NRAMPT activator plays a role in successive aging promotion, while NAMPT is a rate limiting enzyme in NAD+ salvage pathway of Aging/Senescence process[2].
In Vivo: SBI-797812 (10 mg/kg; i.p. or o.p.; single dose) shows high plasma exposure by intraperitoneal injection, with Cmax value of 3297?ng/mL, 8.2?μM.
SBI-797812 (20 mg/kg; i.p.; single dose; measured 2?h post-dose) significant increases NAD+ in mouse liver.