PI3K isoform-selective inhibitors: next-generation targeted cancer therapies
文献类型：期刊论文
| 作者 | Wang, Xiang; Ding, Jian ; Meng, Ling-hua
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2015-10 |
| 卷号 | 36期号:10页码:1170-1176 |
| 关键词 | PI3K isoforms isoform-selective inhibitor CAL101 precise cancer therapy biomarker |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2015.71 |
| 文献子类 | Review |
| 英文摘要 | The pivotal roles of phosphatidylinositol 3-kinases (PI3Ks) in human cancers have inspired active development of small molecules to inhibit these lipid kinases. However, the first-generation pan-PI3K and dual-PI3K/mTOR inhibitors have encountered problems in clinical trials, with limited efficacies as a monotherapeutic agent as well as a relatively high rate of side effects. It is increasingly recognized that different PI3K isoforms play non-redundant roles in particular tumor types, which has prompted the development of isoform-selective inhibitors for pre-selected patients with the aim for improving efficacy while decreasing undesirable side effects. The success of PI3K isoform-selective inhibitors is represented by CAL101 (Idelalisib), a first-in-class PI3Kd-selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin's lymphoma and relapsed small lymphocytic lymphoma. Inhibitors targeting other PI3K isoforms are also being extensively developed. This review focuses on the recent progress in development of PI3K isoform-selective inhibitors for cancer therapy. A deeper understanding of the action modes of novel PI3K isoform-selective inhibitors will provide valuable information to further validate the concept of targeting specific PI3K isoforms, while the identification of biomarkers to stratify patients who are likely to benefit from the therapy will be essential for the success of these agents. |
| WOS关键词 | CHRONIC LYMPHOCYTIC-LEUKEMIA ; CLINICAL-TRIALS ; CELL LINES ; P110-DELTA ; P110-ALPHA ; IDELALISIB ; CAL-101 ; PATHWAY ; POTENT ; MECHANISMS |
| 资助项目 | National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09301-001] ; National Natural Science Foundation of China[81321092] ; National Natural Science Foundation of China[81373445] ; National Natural Science Foundation of China[81402972] ; Science and Technology Commission of Shanghai Municipality[14431905200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5531926 |
| WOS记录号 | WOS:000362459200003 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276384]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Xiang,Ding, Jian,Meng, Ling-hua. PI3K isoform-selective inhibitors: next-generation targeted cancer therapies[J]. ACTA PHARMACOLOGICA SINICA,2015,36(10):1170-1176. |
| APA | Wang, Xiang,Ding, Jian,&Meng, Ling-hua.(2015).PI3K isoform-selective inhibitors: next-generation targeted cancer therapies.ACTA PHARMACOLOGICA SINICA,36(10),1170-1176. |
| MLA | Wang, Xiang,et al."PI3K isoform-selective inhibitors: next-generation targeted cancer therapies".ACTA PHARMACOLOGICA SINICA 36.10(2015):1170-1176. |
入库方式： OAI收割
来源：上海药物研究所
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