Discovery of WS-157 as a highly potent, selective and orally active EGFR inhibitor

EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.

Study on the involvement of microtubule-associated protein l light chain 3B in the inlfammatory response of Kawa-saki disease / 临床儿科杂志

ObjectiveTo investigate the relationship between microtubule-associated protein l light chain 3B (LC3-II) and the inlfammatory response of Kawasaki disease (KD).MethodsThirty-nine cases of acute KD before intravenous admin-istration of immunoglobulin were enrolled. According to the results of echocardiography, the 39 cases were furtherly divided into KD with coronary artery lesion (CAL, 20 cases) group and KD with non-CAL (NCAL, 19 cases) group. At the same time, 12 healthy children were selected as controls. Serum samples were collected and cultured in vitro by human coronary artery endothe-lial cells (HCAEC) for 12 h. The LC3-II protein and mRNA expression of HCAEC were detected by Western-blotting and Q-PCR respectively.ResultsThe LC3-II protein and mRNA expression in CAL group and NCAL group were signiifcantly higher than those in control group, the LC3-II protein and mRNA expression in CAL group was higher than those in NCAL group, and both differences were statistically signiifcant (P<0.05).ConclusionsAutophagy may be involved in the inlfammatory response of KD in acute phase, which may be related to endothelial cell lesions of coronary artery in children with KD.