C1206(C1206) - 药物靶点：HSP90_在研适应症：费城染色体阳性慢性粒细胞白血病_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

HSP90

作用机制

HSP90 抑制剂(Heat shock 90kDa proteins inhibitors)

治疗领域

肿瘤血液及淋巴系统疾病

在研适应症

费城染色体阳性慢性粒细胞白血病

非在研适应症-

原研机构

福建医科大学附属协和医院

在研机构

福建医科大学附属协和医院

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-

关联

100 项与 C1206 相关的临床结果

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100 项与 C1206 相关的转化医学

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100 项与 C1206 相关的专利（医药）

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1

项与 C1206 相关的文献（医药）

2018-04-01·Acta Pharmacologica Sinica1区 · 医学

C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic myeloid leukemia cells in vitro

1区 · 医学

Article

作者: Lin, Qiao-Fa ; Zhu, Li-Ping ; Gao, Ping-Zhang ; Zhou, Yi-Xiang ; Xu, Jian-Hua ; Liu, Bi ; Zhang, Lian-Ru ; Fan, Ying-Juan ; Cai, Fang

4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and antitumor action. In this study we investigated the relationship between C1206-induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence quenching experiments showed that C1206 seemed to bind the middle dimerization domain of Hsp90. The interaction between C1206 and Hsp90 was driven mainly by electrostatic interaction. In in vitro enzyme activity assay, C1206 dose-dependently inhibited Hsp90 ATPase activity with an IC₅₀ value of 4.17 μmol/L. In both imatinib-sensitive K562 chronic myeloid leukemia cells and imatinib-resistant K562/G₀₁ chronic myeloid leukemia cells, C1206 (0.4-3.2 μmol/L) dose-dependently caused the degradation of Hsp90 client proteins and downstream proteins (AKT, MEK, ERK, C-RAF, P-AKT, P-MEK and P-ERK). Furthermore, C1206 (0.4-3.2 μmol/L) dose-dependently induced apoptosis of K562 and K562/G₀₁ cells through triggering mitochondrial pathway. Consistent with this result, C1206 inhibited the proliferation of K562 and K562/G₀₁ cells with IC₅₀ values of 1.10 and 0.60 μmol/L, respectively. These results suggest that C1206 is a novel Hsp90 inhibitor and a promising therapeutic agent for chronic myeloid leukemia.

100 项与 C1206 相关的药物交易

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