AKI-001(AKI-001) - 药物靶点：Aurora A x Aurora B_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Aurora A x Aurora B

作用方式

抑制剂

作用机制

Aurora A抑制剂(丝氨酸/苏氨酸蛋白激酶Aurora-A抑制剂)、Aurora B抑制剂(丝氨酸/苏氨酸蛋白激酶Aurora-B抑制剂)

治疗领域

肿瘤

在研适应症-

非在研适应症

肿瘤

原研机构

Genentech, Inc.

在研机构-

非在研机构

Roche Diagnostics GmbH

Genentech, Inc.

权益机构-

最高研发阶段无进展临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 AKI-001 相关的临床结果

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100 项与 AKI-001 相关的转化医学

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100 项与 AKI-001 相关的专利（医药）

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1

项与 AKI-001 相关的文献（医药）

2008-08-01·Journal of Medicinal Chemistry1区 · 医学

A Pentacyclic Aurora Kinase Inhibitor (AKI-001) with High in Vivo Potency and Oral Bioavailability

1区 · 医学

Article

作者: Liang, Jun ; Halladay, Jason ; Phillips, Gail ; Dotson, Jenna ; Fields, Carter ; Cochran, Andrea G. ; Rüth, Matthias ; Zhu, Bing-Yan ; Rüger, Petra ; Kleinheinz, Tracy ; McNutt, Angela ; Rawson, Thomas E. ; Moffat, John ; Georges, Guy J. ; Limberg, Anja ; Zhou, Aihe ; Wiesmann, Christian ; Safina, Brian ; Blackwood, Elizabeth ; Drummond, Jason ; Walker, Leslie ; Burdick, Dan ; Ran, Yingqing ; Zhang, Birong ; Goller, Bernhard ; Hunsaker, Thomas ; Krell, Hans-Willi ; Ultsch, Mark ; Li, Jun ; Corson, Laura

Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B enzymes, excellent cellular potency (IC50 < 100 nM), and good oral bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B are inhibited at inhibitor concentrations sufficient to block proliferation. Importantly, the cellular activity translates to potent inhibition of tumor growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near stasis (92% TGI) in an HCT116 mouse xenograft model.

100 项与 AKI-001 相关的药物交易

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