OT-82 is a potent, selective, and orally active inhibitor of nicotinamide phosphoribosyltransferase (NAMPT).

NAMPT:

METHODS: OT-82 (0.001-10 μM) was used to treat human cell lines derived from HP and non-HP cancers, and the IC50 values ​​were determined.
RESULTS: The average IC50 of OT-82 was significantly higher in non-HP cancer cells compared with HP cancer cells (13.03±2.94 nM vs 2.89±0.47 nM; p < 0.008). [1]
METHODS: MV4-11 cells were treated with OT-82 (0.001-10 nM), and the changes in NAD were observed for 24 hours, and the changes in ATP were observed for 24 hours and 48 hours.
RESULTS: OT-82 treatment resulted in a dose-dependent decrease in NAD and ATP concentrations in MV4-11 cells. OT-82 treatment of MV4-11 cells in vitro for 48 hours resulted in caspase-3 activation, an increase in the proportion of cells with sub-G1 DNA content, and mitochondrial membrane depolarization. OT-82 induced apoptosis and cell death by inhibiting NAMPT, leading to NAD and ATP depletion. [1]

METHODS: OT-82 (25 or 50 mg/kg) was administered orally 6 days per week for 3 weeks. The therapeutic efficacy of OT-82 was tested in vivo using subcutaneous (SC) and systemic mouse xenograft models of HP malignancies.
RESULTS: OT-82 caused a dose-dependent inhibition of SC growth of human AML-derived MV4-11 cells; the 25 mg/kg dose resulted in a 3-fold reduction in mean tumor volume at day 17 of treatment, while higher doses resulted in complete eradication of tumors within 10 days of treatment initiation. [1]