T3Inh-1 is a potent and selective inhibitor of ppGalNAc-T3 (IC50=7 µM). T3Inh-1 reduces FGF23 hormone levels in both tissue cells and mice, without causing any toxic side effects. T3Inh-1 also prevents breast cancer cells. The enzyme ppGalNAc-T3 is implicated in at least two medically important pathways: cancer metastasis and stabilization of FGF23 (regulates phosphate levels in the bloodstream)[1].
T3Inh-1 (5 µM; 24-48 hours; 5 µM; MDA-MB231 cells) is strikingly effective, inhibiting migration by >80% and invasion by 98% while causing no discernable effect on cell proliferation[1].
T3Inh-1 exhibits no toxicity and did not affect HEK cell proliferation[1].
T3Inh-1 (HEK cells; 6 hours)increases cleavage of FGF23[1].
T3Inh-1 (25 or 50 mg/kg; i.p.) blocks ppGalNAc-T3-mediated glycan-masking of FGF23 thereby increasing its cleavage[1].
| Animal Model: | Wild-type C57BL/6 six to eight week old mice[1] |
| Dosage: | 25 or 50 mg/kg |
| Administration: | Intraperitoneal injection (Dissolved in DMSO at 25 and 50 mg/ml then further diluted with PEG400 to create 5 and 10 mg/ml stocks for injection) |
| Result: | Caused a robust and statistically significant increase the ratio of cleaved/intact FGF23 at the tested 25 and 50 mg/kg concentrations. |
[1]. Song L, et al. Inhibitor of ppGalNAc-T3-mediated O-glycosylation blocks cancer cell invasiveness and lowers FGF23 levels. Elife. 2017;6:e24051. Published 2017 Mar 31.