EC359

EC359 is a potent, selective, high affinity and orally active leukemia inhibitory factor receptor (LIFR) inhibitor with a K_d of 10.2 nM, which directly interacts with LIFR to effectively block LIF/LIFR interactions^[1]. EC359 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. IC50 & Target:Kd: 10.2 nM (leukemia inhibitory factor receptor)^[1] In Vitro:EC359 (0-100 nM; 3 days; BT-549, SUM-159, MDA-MB-231, MDA-MB-468, and HCC1806 cells) treatment reduces cell viability in a dose-dependent manner^[1].
EC359 (20 nM, 25 nM; 72 hours; MDA-MB-231 and BT-549 cells) treatment significantly increases caspase-3/7 activity and Annexin V-positive cells in both MDAMB-231 and BT-549 cells. EC359 exhibits significant inhibitory activity on invasion and promotes apoptosis of TNBC cells^[1].
EC359 (100 nM; 12 hours; BT549 cells) treatment significantly reduces the expression of several (such as STAT1 TGFB1, JUNB, MCL-1, etc) known STAT3 target genes^[1].
EC359 (100 nM; 1 hour; MDA-MB-231 and BT-549 cells) treatment substantially reduces the LIF activation of STAT3, also reduces the STAT3 activation by OSM and CNTF. EC359 treatment substantially decreases the phosphorylation of AKT, mTOR, S6, and ERK1/2 in MDA-MB231 and BT-549 cells. EC359 treatment also increases the phosphorylation of proapoptotic p38MAPK in BT549 cells^[1]. In Vivo:EC359 (5 mg/kg; subcutaneous injection; 3 days per week; for 25 days; female athymic nude mice) treatment significantly reduces the tumor progression. The body weights of mice in EC359-treated groups remains unchanged confirming the low toxicity of EC359^[1].