SBI-797812 is a NAMPT activator which is structurally similar to active-site directed NAMPT inhibitors and blocks binding of these inhibitors to NAMPT. SBI-797812 turns NAMPT into a "super catalyst" that more efficiently generates NMN.
SBI-797812 shifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT at His247, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD+. Treatment of cultured cells with SBI-797812 increases intracellular NMN and NAD+.[1]
Plasma concentrations of SBI-797812 after oral administration are low. Higher plasma levels of SBI-797812 are seen after i.p. dosing. The potency of SBI-797812 against mouse NAMPT is investigated. The apparent affinity (EC50) of SBI-797812 for mouse NAMPT is approximately 8-fold less than for human NAMPT, whereas maximal fold activation by SBI-797812 is comparable between the mouse and human NAMPT. Dosing of mice with SBI-797812 elevates liver NAD+.[1]
[1] Stephen J Gardell, et al. Nat Commun. 2019 Jul 19;10(1):3241.