| Identification | Back Directory | [Name]
SBI-797812 | [CAS]
2237268-08-3 | [Synonyms]
SBI-797812
Urea, N-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-ylsulfonyl)phenyl]-N'-(4-pyridinylmethyl)- | [Molecular Formula]
C19H22N4O4S | [MOL File]
2237268-08-3.mol | [Molecular Weight]
402.47 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [color ]
Light yellow to yellow | [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)/t16-,17+ | [InChIKey]
KTSOHNHLOLGQCY-CALCHBBNSA-N | [SMILES]
O=C(NC1=CC=C(S(=O)(N(C2)C[C@H]3O[C@@H]2CC3)=O)C=C1)NCC4=CC=NC=C4 |
| Hazard Information | Back Directory | [Uses]
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]. | [Biochem/physiol Actions]
SBI-797812 is a cell penetrant and potent activator of nicotinamide phosphoribosyltransferase (NAMPT) that increases intracellular levels of NMN and NAD+ in cells. SBI-797812 blocks binding of inhibitors to NAMPT and shifts the reaction equilibrium towards NMN formation. It elevates levels of NAD+ in mice liver. | [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[1].
?
SBI-797812 (20 mg/kg; i.p.; single dose; measured 2?h post-dose) significant increases NAD+ in mouse liver[1].
| Animal Model: | Male C57BL/6?J mice (8-week-old)[1] | | Dosage: | 20 mg/kg | | Administration: | Intraperitoneal injection; administrated 1 h after fasting; added Buthanasia-D (165?mg/kg; i.p.) 4 h after fasting | | Result: | Showed 0.311, 0.144, 0.078, and 0.078?μg/mg dry powder about NAD+ in liver, heart, gastrocnemius and quadriceps, respectively by LC-MS/MS measurement.
|
| [References]
[1] Gardell SJ , et al. Boosting NAD+ with a small molecule that activates NAMPT. Nat Commun. 2019 Jul 19;10(1):3241. DOI:10.1038/s41467-019-11078-z
[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. DOI:10.3390/ijms22073709 |
|
|