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作为丝氨酸/苏氨酸蛋白激酶调节剂和抑制剂的天然化合物及其衍生物

Natural Compounds and Derivatives as Ser/Thr Protein Kinase Modulators and Inhibitors.

作者信息

Guerra Barbara, Issinger Olaf-Georg

机构信息

Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.

出版信息

Pharmaceuticals (Basel). 2019 Jan 1;12(1):4. doi: 10.3390/ph12010004.

Abstract

The need for new drugs is compelling, irrespective of the disease. Focusing on medical problems in the Western countries, heart disease and cancer are at the moment predominant illnesses. Owing to the fact that ~90% of all 21,000 cellular proteins in humans are regulated by phosphorylation/dephosphorylation it is not surprising that the enzymes catalysing these reactions (i.e., protein kinases and phosphatases, respectively) have attracted considerable attention in the recent past. Protein kinases are major team players in cell signalling. In tumours, these enzymes are found to be mutated disturbing the proper function of signalling pathways and leading to uncontrolled cellular growth and sustained malignant behaviour. Hence, the search for small-molecule inhibitors targeting the altered protein kinase molecules in tumour cells has become a major research focus in the academia and pharmaceutical companies.

摘要

无论针对何种疾病,对新药的需求都极为迫切。聚焦于西方国家的医学问题,心脏病和癌症目前是主要疾病。鉴于人类所有21000种细胞蛋白中约90%受磷酸化/去磷酸化调控,催化这些反应的酶(即分别为蛋白激酶和磷酸酶)在最近受到相当大的关注也就不足为奇了。蛋白激酶是细胞信号传导中的主要参与者。在肿瘤中,发现这些酶发生突变,扰乱了信号通路的正常功能,导致细胞不受控制地生长和持续的恶性行为。因此,寻找靶向肿瘤细胞中改变的蛋白激酶分子的小分子抑制剂已成为学术界和制药公司的主要研究重点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e23/6469162/281d7e192e45/pharmaceuticals-12-00004-g001.jpg

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