Puquitinib, a novel orally available PI3K inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia
文献类型：期刊论文
| 作者 | Xie, Chengying ; He, Ye; Zhen, Mingyue; Wang, Yulan; Xu, Yongping; Lou, Liguang
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| 刊名 | CANCER SCIENCE
 |
| 出版日期 | 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. |
| WOS关键词 | CHRONIC LYMPHOCYTIC-LEUKEMIA ; PHOSPHOINOSITIDE 3-KINASE DELTA ; SELECTIVE INHIBITORS ; B-CELLS ; ISOFORM ; CANCER ; P110-DELTA ; PI3K-DELTA ; PATHWAY ; PROTEIN |
| 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研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000404963700023 |
| 出版者 | WILEY |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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