1.Correlation research of myeloperoxidase and the severity of coronary lesions in patients with acute coronary syndrome
Qinghua MA ; Ming PAN ; Zheng ZHANG ; Xingrong LIU ; Xiping SHEN ; Aiyun DENG ; Ming BAI ; Rong ZHOU ; Zhilu WANG
Chinese Journal of Postgraduates of Medicine 2011;34(34):12-15
ObjectiveTo research the relationship between the plasma levels of myeloperoxidase (MPO) and the onset and progress of acute coronary syndrome (ACS) and the severity of coronary lesions in patients with ACS.MethodsSeventy-eight patients hospitalized with chest pain were enrolled,including 41 patients with ACS (ACS group),17 patients with stable angina pectoris(SAP,SAP group) and 20 patients serving as control (control group).Forty-one patients undergoing coronary angiography were divided into single vessel lesions group (7 patients),double vessel lesions group (7 patients),multiple vessel lesions group ( 12 patients) and no vessel lesions group ( 15 patients) based on the vessel lesions of the left anterior descending,left circumflex artery and right coronary artery.According to the diameter stenosis of major coronary artery,there were 15 patients in no vascular stenosis group,2 patients in mild vascular stenosis group,6 patients in moderate vascular stenosis group and 18 patients in severe vascular stenosis group.The levels of MPO were measured by enzyme-linked immunosorbent assays(ELISA).ResultsThe levels of MPO in ACS group [( 252.10 ± 27.07 ) μ g/L]were higher than those in SAP group[( 185.81 ± 17.85 ) μ g/L]and control group [( 140.42 ± 71.40) μ g/L](P < 0.05 ),the levels of MPO in SAP group were higher than those in control group(P< 0.05 ).The levels of MPO in single vessel lesions group and multiple vessel lesions group were higher than those in no vessel lesions group (P < 0.05 ),but there was no significant difference among single vessel lesions group,double vessel lesions group and multiple vessel lesions group (P > 0.05 ).The levels of MPO in mild vascular stenosis group,moderate vascular stenosis group and severe vascular stenosis group were higher than those in no vascular stenosis group (P < 0.05),but there was no significant differenceamong mild vascular stenosis group,moderate vascular stenosis group and severe vascular stenosis group(P > 0.05 ).A positive correlation was observed between the levels of MPO and neutrophils (r =0.288,P=0.018 ),creatine kinase isoenzyme-MB(r =0.469,P=0.043 ),subject groups( r =0.757,P=0.000),vessel lesions (r =0.584,P=0.000) and the degree of vascular stenosis (r =0.491,P=0.001).Conclusion MPO may predict ACS and reflect the severity of coronary lesions in ACS as a novel inflammatory marker.
2.Discovery of WS-157 as a highly potent, selective and orally active EGFR inhibitor.
Pengxing HE ; Shenghui NIU ; Shuai WANG ; Xiaojing SHI ; Siqi FENG ; Linna DU ; Xuyang ZHANG ; Zhilu MA ; Bin YU ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(6):1193-1203
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.