YXG-158(YXG-158) - 药物靶点：AR x CYP17A1_在研适应症：前列腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

AR x CYP17A1

作用机制

AR拮抗剂(雄激素受体拮抗剂)、CYP17A1抑制剂(类固醇17-α-羟化酶抑制剂)

治疗领域

肿瘤泌尿生殖系统疾病

在研适应症

前列腺癌

非在研适应症-

原研机构

中国科学院

在研机构

中国科学院

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)临床前

特殊审评-

结构

分子式C30H36FN3O

InChIKeyJHVKBJJTUMIPIT-QQKFYDJZSA-N

CAS号-

关联

100 项与 YXG-158 相关的临床结果

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100 项与 YXG-158 相关的转化医学

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100 项与 YXG-158 相关的专利（医药）

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1

项与 YXG-158 相关的文献（医药）

2023-07-27·Journal of medicinal chemistry1区 · 医学

Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer.

1区 · 医学

Article

作者: Wang, Ao ; Chen, Kaixian ; Lu, Zhengyu ; Meng, Xin ; Luo, Xianggang ; Yang, Yushe

The androgen/androgen receptor (AR) signaling pathway plays an important role in castration-resistant prostate cancer (CRPC). Bifunctional agents that simultaneously degrade AR and inhibit androgen synthesis are expected to block the androgen/AR signaling pathway more thoroughly, demonstrating the promising therapeutic potential for CRPC, even enzalutamide-resistant CRPC. Herein, a series of steroid analogs were designed, synthesized, and identified as selective AR degraders, among which YXG-158 (23-h) was the most potent antitumor compound with dual functions of AR degradation and CYP17A1 inhibition. In addition, 23-h abrogated the hERG inhibition and exhibited excellent PK profiles. In vivo, 23-h effectively inhibited the growth of hormone-sensitive organs in the Hershberger assay and exhibited robust antitumor efficacy both in enzalutamide-sensitive (LNCaP/AR) and enzalutamide-resistant (C4-2b-ENZ) xenograft models. Thus, 23-h was chosen as a preclinical candidate for the treatment of enzalutamide-resistant prostate cancer.

100 项与 YXG-158 相关的药物交易

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