M435-1279

M435-1279 is a UBE2T inhibitor. M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> E1/E2/E3 Enzyme

UBE2T

M435-1279 (0, 2, 4, 8, 16, 31 μM; 48 h) significantly inhibits the growth of HGC27, AGS, and MKN45 cells[1]. M435-1279 (0, 4, 8, 12, 16, 20 μM) inhibits the cell viability whit a IC50 s of 16.8, 11.88, 6.93, 7.76 μM of GES-1, HGC27, MKN45, AGS cells, respectively[1]. M435-1279 (31 nM to 500 μM) binding to UBE2T whit a KD value of 50.5 μM[1]. M435-1279 has high LD50 (15.6 g/kg), LOAEL (0.207g/kg), and has a EC50 value of 7.47mg/L[1]. M435-1279 (11.88  μM; 48 h) inhibits the ubiquitination of RACK1 and the hyperactivation of the Wnt/β-catenin pathway[1]. Cell Viability Assay[1] Cell Line: HGC27, AGS, and MKN45 cells Concentration: 0, 2, 4, 8, 16, 31 μM Incubation Time: 48 h Result: Inhibited the cell growth. Cell Viability Assay[1] Cell Line: HGC27, AGS, and MKN45 cells Concentration: 0, 4, 8, 12, 16, 20 μM Incubation Time: Result: Inhibited the cell viability whit a IC50s of 16.8, 11.88, 6.93, 7.76 μM in GES-1, HGC27, MKN45, AGS cells, respectively.

M435-1279 (5 mg/kg/day; intratumor injections for 18 days) slows the tumor growth. M435-1279 induces higher RACK1 proteins expression, and lower Ki-67 and β-catenin proteins expression in intratumor tumors[1]. Animal Model: BALB/C nude mice CDX model (MKN45 tumor size: 75–100 mm3) [1] Dosage: 5 mg/kg/day Administration: intratumor injections for 18 days Result: Slowed the tumor growth. Induced higher RACK1 proteins expression, and lower Ki-67 and β-catenin proteins expression in intratumor tumors.

[1]. [1] Yu Z, et al. A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. Oncogene. 2021 Feb;40(5):1027-1042. doi: 10.1038/s41388-020-01572-w. Epub 2020 Dec 15. Erratum in: Oncogene. 2021 Apr;40(14):2622-2623.