HS-438(HS-438) - 药物靶点：Bcr-Abl T315I_在研适应症：BCR/ABL阴性非典型性慢性髓系白血病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Bcr-Abl T315I

作用机制

Bcr-Abl T315I抑制剂(bcr-abl酪氨酸激酶T315I抑制剂)

治疗领域

肿瘤血液及淋巴系统疾病其他疾病

在研适应症

BCR/ABL阴性非典型性慢性髓系白血病

非在研适应症-

原研机构

Inha University

在研机构

Inha University

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-

结构

分子式C17H17N3O3S

InChIKeyLAAHHHDILCOULN-UHFFFAOYSA-N

CAS号1430720-10-7

关联

100 项与 HS-438 相关的临床结果

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100 项与 HS-438 相关的转化医学

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100 项与 HS-438 相关的专利（医药）

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1

项与 HS-438 相关的文献（医药）

2014-06-01·Cancer Letters1区 · 医学

HS-438, a new inhibitor of Imatinib-resistant BCR-ABL T315I mutation in chronic myeloid leukemia

1区 · 医学

Article

作者: Kim, JinHee ; Son, Mi Kwon ; Kim, Soo Jung ; Hong, Sungwoo ; Shin, Sanghye ; Lee, Hyunseung ; Fang, Zhenghuan ; Yan, Hong Hua ; Yun, Sun-Mi ; Hong, Soon-Sun ; Jung, Kyung Hee

Imatinib is a selective breakpoint cluster region-Abelson (BCR-ABL) tyrosine kinase inhibitor (TKI) that has significantly improved the prognosis of patients with chronic myeloid leukemia (CML). However, T315I gene mutations of the BCR-ABL kinase domain have been shown to confer resistance to imatinib. In the present study, we synthesized a novel BCR-ABL inhibitor, HS-438, and identified its anti-leukemic effects in vitro and in vivo. We found that HS-438 strongly inhibited the expression of BCR-ABL signaling pathways in wild-type BCR-ABL (BaF3/WT) cells as well as T315I-mutated BCR-ABL (BaF3/T315I) cells with resistance to imatinib. HS-438 induced cell cycle arrest, particularly during the G0/G1 cell cycle phase, and induced apoptosis. In BaF3/T315I xenograft models, HS-438 significantly delayed tumor growth, unlike imatinib. In summary, we suggest that HS-438 may be a novel drug candidate with the therapeutic potential to target BCR-ABL and overcome imatinib resistance in patients with CML.

100 项与 HS-438 相关的药物交易

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