ABC-1183(ABC-1183) - 药物靶点：CDK9 x GSK-3α x GSK-3β_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

CDK9 x GSK-3α x GSK-3β

作用机制

CDK9抑制剂(细胞周期蛋白依赖性激酶9抑制剂)、GSK-3α抑制剂(glycogen synthase kinase 3 alpha inhibitors)、GSK-3β抑制剂(糖原合酶激酶-3β抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Apogee Biotechnology Corp.

在研机构

Apogee Biotechnology Corp.

非在研机构-

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 ABC-1183 相关的临床结果

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100 项与 ABC-1183 相关的转化医学

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100 项与 ABC-1183 相关的专利（医药）

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1

项与 ABC-1183 相关的文献（医药）

2018-04-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

In Vitro and In Vivo Antitumor and Anti-Inflammatory Capabilities of the Novel GSK3 and CDK9 Inhibitor ABC1183

3区 · 医学

Article

作者: Keller, Staci N ; Green, Cecelia L ; Smith, Ryan A ; Maines, Lynn W ; Smith, Charles D ; Schrecengost, Randy S ; Zhuang, Yan

Glycogen synthase kinase-3s (GSK3α and GSK3β) are constitutively active protein kinases that target over 100 substrates, incorporate into numerous protein complexes, and regulate such vital cellular functions as proliferation, apoptosis, and inflammation. Cyclin-dependent kinase 9 (CDK9) regulates RNA production as a component of positive transcription elongation factor b and promotes expression of oncogenic and inflammatory genes. Simultaneous inhibition of these signaling nodes is a promising approach for drug discovery, although previous compounds exhibit limited selectivity and clinical efficacy. The novel diaminothiazole ABC1183 is a selective GSK3α/β and CDK9 inhibitor and is growth-inhibitory against a broad panel of cancer cell lines. ABC1183 treatment decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, glycogen synthase, and β-catenin phosphorylation and MCL1 expression. Oral administration, which demonstrates no organ or hematologic toxicity, suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms, owing in part to downregulation of tumor necrosis factor α and interleukin-6 proinflammatory cytokines. Therefore, ABC1183 is strategically poised to effectively mitigate multiple clinically relevant diseases.

100 项与 ABC-1183 相关的药物交易

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