SBI-797812

• CAT Number: I018690
• CAS Number: 2237268-08-3
• Molecular Formula: C19H22N4O4S
• Molecular Weight: 402.47
• Purity: ≥95%
• Synonyms: 1-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-ylsulfonyl)phenyl]-3-(pyridin-4-ylmethyl)urea
• InChI: InChI=1S/C19H22N4O4S/c24-19(21-11-14-7-9-20-10-8-14)22-15-1-5-18(6-2-15)28(25,26)23-12-16-3-4-17(13-23)27-16/h1-2,5-10,16-17H,3-4,11-13H2,(H2,21,22,24)
• InChIKey: KTSOHNHLOLGQCY-UHFFFAOYSA-N
• SMILES: C1CC2CN(CC1O2)S(=O)(=O)C3=CC=C(C=C3)NC(=O)NCC4=CC=NC=C4

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[1][2].
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[1].
SBI-797812 (2 μM; 1 or 4 h) exerts NAMPT (30 nM) activation requiring ATP (2 mM)[1].
SBI-797812 (5 μM; 2 h) impacts PP (20 μM) consumption and pHisNAMPT reactivity[1].
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[1].
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].
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[1].
SBI-797812 (20 mg/kg; i.p.; single dose; measured 2 h post-dose) significant increases NAD+ in mouse liver[1].

Reference

[1]. Gardell SJ , et al. Boosting NAD+ with a small molecule that activates NAMPT. Nat Commun. 2019 Jul 19;10(1):3241.
 [Content Brief]

[2]. Khaidizar FD, et al. Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process. Int J Mol Sci. 2021 Apr 2;22(7):3709. 
 [Content Brief]