NAMPT activator-3, a NAT derivative, is a NAMPT activator with an EC50 of 2.6 μM and a KD of 132 nM. NAMPT activator-3 effectively protects cultured cells from FK866 -mediated toxicity. NAMPT activator-3 exhibits strong neuroprotective efficacy in a chemotherapy-induced peripheral neuropathy (CIPN) mouse model without any overt toxicity.
NAMPT activator-3 (compound 72; 0.1, 0.3, 1, 3, 10 μM; 72 hours) exertes no side effect on the cell viability including osteosarcoma cells (U2OS), glioblastoma cells (T98G), neuroblastoma cells (SH-SY5Y) and liver carcinoma cells (HepG2)[1].
NAMPT activator-3 (compound 72) protects peripheral sensory neurons from Taxol -induced damage by enhancing NAD production[1].
Pharmacokinetic Parameters of NAMPT activator-3 in mice[1].
| IV (1 mg/kg) | IP (30 mg/kg) | PO (30 mg/kg) | |
| Tmax (h) | 0.25 | ||
| Cmax (ng/mL) | 1563 | 188 | |
| AUClast (h∗ng/mL) | 183 | 1333 | 388 |
| T1/2 (h) | 0.18 | 1.05 | 1.34 |
| CL (mL/min/kg) | 90.4 | ||
| Vss (mL/kg) | 1130 | ||
| F (%) | 24.2 | 7.05 |
References:
[1]. Leibo Wang, et al. Optimization of NAMPT activators to achieve in vivo neuroprotective efficacy. Eur J Med Chem. 2022 Jun 5;236:114260.