TNP-470

TNP-470 is a methionine aminopeptidase-2 inhibitor and also an angiogenesis inhibitor. IC50 & Target: methionine aminopeptidase-2^[1], angiogenesis^[2] In Vitro: No significant difference of apoptotic cell numbers is observed between cells treated with TNP-470 and the controls. The IC₅₀s of TNP-470 are 16.86±0.9 µg/mL, 3.16±0.6 µg/mL and 1.78±0.8 µg/mL for KKU-M213 cells at 24, 48 and 72 h, respectively. The results show that TNP-470 significantly reduces the number of migrated cells and invaded cells as compare with the vehicle treated group. TNP-470 decreases the migrated cells of KKU-M213 to 26% and of KKU-M214 to 11% (P<0.01). Similarly, TNP-470 also significantly affects cell invasion, the number of invaded cells is reduced to 25% in KKU-M213 (P<0.01) and to 15% in KKU-M214 (P<0.01). The relative expressions of MMP2, MMP9 and c-MYC in TNP-470 treated cells are significantly suppressed compare to the vehicle treated cells^[1]. In Vivo: Treatment with TNP-470 attenuates (P<0.05) liver lipid accumulation compare to high fat fed (HFF) mice. By day 5, TNP-470 treated mice consume significantly less grams of high fat food than vehicle treated HFF mice. By day 15 of treatment, TNP-470 mice are consuming an equivalent number of calories to that of chow fed mice, despite the provision of high fat diet. Treatment with TNP-470 increases (P<0.05) expression of adipose tissue LPL mRNA, compare to chow-fed and high-fat fed controls. TNP-470 decreases energy intake and increases energy expenditure^[2].