Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia

doi:10.1111/cas.13263

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

	Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia
	Xie, Chengying; He, Ye; Zhen, Mingyue; Wang, Yulan; Xu, Yongping; Lou, Liguang
刊名	CANCER SCIENCE
	2017-07
卷号	108 期号:7 页码:1476-1484
关键词	Acute myeloid leukemia CAL-101 PI3K signaling PI3K puquitinib
ISSN号	1349-7006
DOI	10.1111/cas.13263
文献子类	Article
英文摘要	The PI3K isoform (PIK3CD), also known as P110, is predominately expressed in leukocytes and has been implicated as a potential target in the treatment of hematological malignancies. In this report, we detailed the pharmacologic properties of puquitinib, a novel, orally available PI3K inhibitor. Puquitinib, which binds to the ATP-binding pocket of PI3K, was highly selective and potent for PI3K relative to other PI3K isoforms and a panel of protein kinases, exhibiting low-nanomolar biochemical and cellular inhibitory potencies. Additional cellular profiling demonstrated that puquitinib inhibited proliferation, induced G(1)-phase cell-cycle arrest and apoptosis in acute myeloid leukemia (AML) cell lines, through downregulation of PI3K signaling. In in vivo AML xenografts, puquitinib alone showed stronger efficacy than the well-known p110 inhibitor, CAL-101, in association with a reduction in AKT and ERK phosphorylation in tumor tissues, without causing noticeable toxicity. Furthermore, the combination of puquitinib with cytotoxic drugs, especially daunorubicin, yielded significantly stronger antitumor efficacy compared with each agent alone. Thus, puquitinib is a promising agent with pharmacologic properties that are favorable for the treatment of AML.
资助项目	National Natural Science Foundation of China[30801404] ; National Natural Science Foundation of China[81273546] ; National Key Research & Development Plan[2016YFC1201003]
WOS关键词	CHRONIC LYMPHOCYTIC-LEUKEMIA ; PHOSPHOINOSITIDE 3-KINASE DELTA ; SELECTIVE INHIBITORS ; B-CELLS ; ISOFORM ; CANCER ; P110-DELTA ; PI3K-DELTA ; PATHWAY ; PROTEIN
WOS研究方向	Oncology
语种	英语
出版者	WILEY
WOS记录号	WOS:000404963700023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272590]
专题	药理学第一研究室
通讯作者	Lou, Liguang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xie, Chengying,He, Ye,Zhen, Mingyue,et al. Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia[J]. CANCER SCIENCE,2017,108(7):1476-1484.
APA	Xie, Chengying,He, Ye,Zhen, Mingyue,Wang, Yulan,Xu, Yongping,&Lou, Liguang.(2017).Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia.CANCER SCIENCE,108(7),1476-1484.
MLA	Xie, Chengying,et al."Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia".CANCER SCIENCE 108.7(2017):1476-1484.