PI3K isoform-selective inhibitors: next-generation targeted cancer therapies

doi:10.1038/aps.2015.71

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	PI3K isoform-selective inhibitors: next-generation targeted cancer therapies
	Wang, Xiang; Ding, Jian; Meng, Ling-hua
刊名	ACTA PHARMACOLOGICA SINICA
	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.
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关键词	CHRONIC LYMPHOCYTIC-LEUKEMIA ; CLINICAL-TRIALS ; CELL LINES ; P110-DELTA ; P110-ALPHA ; IDELALISIB ; CAL-101 ; PATHWAY ; POTENT ; MECHANISMS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5531926
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000362459200003
内容类型	期刊论文
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.