SP-96(SP-96) - 药物靶点：Aurora B_在研适应症：三阴性乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Aurora B

作用机制

Aurora B抑制剂(丝氨酸/苏氨酸蛋白激酶Aurora-B抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症

三阴性乳腺癌

非在研适应症-

原研机构

University of Arkansas System

在研机构

University of Michigan

非在研机构

University of Arkansas System

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SP-96 相关的临床结果

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100 项与 SP-96 相关的转化医学

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100 项与 SP-96 相关的专利（医药）

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1

项与 SP-96 相关的文献（医药）

2020-10-01·European Journal of Medicinal Chemistry1区 · 医学

Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression

1区 · 医学

Article

作者: Belachew, Binyam ; Lakkaniga, Naga Rajiv ; Gunaganti, Naresh ; Frett, Brendan ; Zhang, Lingtian ; Li, Hong-Yu

Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B enzymatic assays (IC₅₀ = 0.316 ± 0.031 nM). We identified the important pharmacophore features resulting in selectivity against receptor tyrosine kinases. Particularly, SP-96 shows >2000 fold selectivity against FLT3 and KIT which is important for normal hematopoiesis. This could diminish the adverse effect of neutropenia reported in the clinical trials of the Aurora B inhibitor Barasertib, which inhibits FLT3 and KIT in addition to Aurora B. Enzyme kinetics of SP-96 shows non-ATP-competitive inhibition which makes it a first-in-class inhibitor. Further, SP-96 shows selective growth inhibition in NCI60 screening, including inhibition of MDA-MD-468, a Triple Negative Breast Cancer cell line.

100 项与 SP-96 相关的药物交易

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