G-5758(G-5758) - 药物靶点：IRE1_在研适应症：多发性骨髓瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

IRE1

作用方式

抑制剂

作用机制

IRE1抑制剂(丝氨酸/苏氨酸 - 蛋白激酶/内切核糖核酸酶肌醇需要酶1抑制剂)

治疗领域

肿瘤免疫系统疾病心血管疾病+ [1]

在研适应症

多发性骨髓瘤

非在研适应症-

原研机构

Genentech, Inc.

在研机构

Genentech, Inc.

非在研机构-

权益机构-

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-

结构/序列

分子式C27H24F4N6O3S

InChIKeyRBOAUACOQMQNBF-ROUUACIJSA-N

CAS号2413455-99-7

关联

100 项与 G-5758 相关的临床结果

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100 项与 G-5758 相关的转化医学

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100 项与 G-5758 相关的专利（医药）

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1

项与 G-5758 相关的文献（医药）

2024-06-13·Journal of Medicinal Chemistry

Discovery of Potent, Selective, and Orally Available IRE1α Inhibitors Demonstrating Comparable PD Modulation to IRE1 Knockdown in a Multiple Myeloma Model

Article

作者: Kaufman, Susan ; Wallweber, Heidi Ackerly ; Gibbons, Paul ; De Bruyn, Tom ; Jiang, Fan ; Rudolph, Joachim ; Zhao, Liang ; Braun, Marie-Gabrielle ; Clark, Kevin R ; Lemire, Alexandre ; Beveridge, Ramsay E ; Leclerc, Jean-Philippe ; Ashkenazi, Avi ; Wei, Wentao ; Ly, Cuong ; Fu, Liqiang ; Sims, Jessica ; Wang, Weiru ; Beresini, Maureen H ; Kiefer, James R ; Segal, Ehud ; Castanedo, Georgette ; Schwarz, Jacob B ; Kan, David

The lack of selective and safe in vivo IRE1α tool molecules has limited the evaluation of IRE1α as a viable target to treat multiple myeloma. Focus on improving the physicochemical properties of a literature compound by decreasing lipophilicity, molecular weight, and basicity allowed the discovery of a novel series with a favorable in vitro safety profile and good oral exposure. These efforts culminated in the identification of a potent and selective in vivo tool compound, G-5758, that was well tolerated following multiday oral administration of doses up to 500 mg/kg. G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown as measured by XBP1s levels in a multiple myeloma model (KMS-11).

100 项与 G-5758 相关的药物交易

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