ES-072

Description: ES-072, a selective inhibitor targeting the EGFR mutant (EGFR-T790M), is administered orally. By hindering EGFR-T790M activity, it activates GSK3alpha, which subsequently leads to the phosphorylation of PD-L1 at Ser279 and Ser283. This phosphorylation facilitates the recruitment of the E3 ubiquitin ligase ARIH1, resulting in the ubiquitination and proteasomal degradation of PD-L1. Such a process not only curtails the growth of cancer cells but also amplifies the anti-tumor immune response by diminishing PD-L1 levels. ES-072 has shown efficacy in impeding the proliferation of non-small cell lung cancer (NSCLC) cells. Target: PD-1/PD-L1, EGFR, GSK-3. Smiles: O=C(C=C)NC1=CC=CC(=C1)NC2=NC(=NC=C2C(F)(F)F)NC=3C=CC(=NC3OC)N4CCN(C)CC4