| 1 | Development of small molecule extracellular signal-regulated kinases(ERKs) inhibitors for cancer therapy显示文摘The mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase 1/2(ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance. | Xiaoli Pan Junping Pei Aoxue Wang Wen Shuai Lu Feng Faqian Bu Yumeng Zhu Lan Zhang Guan Wang Liang Ouyang | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 4 |
| 2 | Composition analysis of acid hydrolysates from Cucurbita moschata Duch.polysaccharides and their effect on oxidative stress resistance of Caenorhabditis elegans显示文摘Pumpkin polysaccharides(PPe)have a variety of bioactive effects and our previous research showed the acid hydrolysate(PPe-S,a mixture)from PPe had an antioxidative capacity both in vitro and in viro.The aim of this study was to purify PPe-S and investigate the antioxidant stress effects of 2 purified components(PPe-S-1 and PPe-S-2)using Caenorhabditis elegans as model organism.The results showed that PPe-S-2 had a notable antioxidant effect,and could significantly enhance the activities of antioxidant enzymes including superoxide dismutase(SOD)(P<0.01),catalase(CAT)(P<0.01)and glutathione reductase(GR)(P<0.05),and increase the level of glutathione(GSH)(P<0.01),and decreased the content of malondialdehyde(MDA)(P<0.05).PPe-S-2 could significantly extend the survival time of C.elegans(P<0.01),which were stress-induced by hydrogen peroxide and methyl viologen.PPe-S-2 was a heteropolys accharide composed of glucose,arabinose,rhamnose and galactose with the molar ratio of 1.00:0.03:0.02:0.14.The molecular weight of PPe-S-2 was 0.73 kDa detected by high performance liquid chromatography.These studies demonstrated that PPe-S-2 obtained by the acid hydrolysis of PPe had a prominent protective effect to the damage induced by the intracellular free radical generating agents. | Wen Jiang Yakun Zhang Jiangying Zeng Jing Yao Aoxue Lu Zhiyu Fang Ge Wang Weimin Wang Yongjun Zhang | 2023 | Food Science and Human Wellness2023，12，3： | 0 |
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