Novel Indazole-Based Derivatives as PI3K/mTOR Dual Inhibitors

来源 :第九届IUPAC化学生物学国际研讨会暨第八届世界华人药物化学研讨会 | 被引量 : 0次 | 上传用户：ntyiran

【摘要】

：

【作者】

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Huayong Zhou Jingkang Shen Yi Wang Lanping Ma Xin Wang Lin Chen Yi Chen Jian Ding Tao Meng Linhua Meng

【机构】

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State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Scienc

【出处】

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第九届IUPAC化学生物学国际研讨会暨第八届世界华人药物化学研讨会

【发表日期】

：

2012年8期

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　　Phosphoinositide-3-kinase(PI3K) has attracted vast attention as a promising target for cancer therapeutics because the deregulation of the PI3K/Akt/mTOR signaling pathway is frequently observed in a wide variety of human cancers.A series of indazole-based derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor ZHY147.ZHY147 has shown good physical properties and PK parameters,low nanomolar potency against PI3Kα(IC50=21 nM) and mTOR(IC50=3.6 nM),and excellent inhibition of cell proliferation in human cancer cell lines such as Rh30(IC50=0.287 μM),U87MG(IC50=0.338 μM),A549(IC50=0.140 μM) and LNCap(IC50=0.131 μM).In addition,ZHY147 showed good in vivo efficacy in U87MG tumor xenograft model.

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Novel Indazole-Based Derivatives as PI3K/mTOR Dual Inhibitors

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