详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.

9| 认领 | 导出 | 链接全文 |

文献详情

资源类型：

WOS体系：

Pubmed体系：

收录情况： ◇ SCIE

作者：

机构： [1]International Cooperative Laboratory of Traditional ChineseMedicineModernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China [2]Department of Hematology, Zhujiang Hospital, Southern Medical University, No. 253 GongYeDaDaoZhong, Guangzhou, Guangdong, 510280, China [3]Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China

出处：

DOI：

ISSN：

摘要：

GZD824 is a novel third-generation BCR-ABL inhibitor. It entered Phase II clinical trials in China and Phase Ib clinical trials in USA in 2019 for treatment of patients with resistant chronic myeloid leukemia (CML). We found that at concentrations below 10 nM, GZD824 significantly suppresses FLT3, FGFR1 and PDGFRα kinase activities and inhibits their signal pathways in MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa leukemia cells. It selectively inhibits the growth of MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa cells, and also effectively suppresses the growth of Ba/F3-FLT3-ITD cells harboring F691I and other mutations with IC50 values <10 nM. GZD824 induces G0/G1 phase arrest and apoptosis in MV4-11, KG-1 and EOL-1 cells and activates cleavage of caspase-3 and PARP. In MV4-11, Ba/F3-ITD-F691I and KG-1 mouse xenograft models, GZD824 at 10 or 20 mg/kg, q2d, p.o. almost completely eradicates tumors. It also inhibits the viability of primary leukemic blasts from a FLT3-ITD positive AML patient but not those expressing native FLT3. Thus GZD824 suppresses leukemia cells of FLT3-ITD-driven AML and other hematologic malignancies driven by FGFR1 or PDGFRa, and it may be considered to be a novel agent for the treatment of leukemia. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

语种：

WOS：

PubmedID：

中科院(CAS)分区：

出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2025]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

JCR分区：

出版当年[2018]版：

Q2 ONCOLOGY

最新[2023]版：

Q1 ONCOLOGY

影响因子： 4.5 最新[2023版] 4.2 最新五年平均 3.138 出版当年[2018版] 3.308 出版当年五年平均 3.071 出版前一年[2017版] 3.558 出版后一年[2019版]

第一作者：

第一作者机构： [1]International Cooperative Laboratory of Traditional ChineseMedicineModernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China

共同第一作者：

通讯作者：

通讯机构： [1]International Cooperative Laboratory of Traditional ChineseMedicineModernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China [2]Department of Hematology, Zhujiang Hospital, Southern Medical University, No. 253 GongYeDaDaoZhong, Guangzhou, Guangdong, 510280, China [*1]International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. [*2]Department of Hematology, Zhujiang Hospital, Southern Medical University, No. 253 GongYeDaDaoZhong, Guangzhou, Guangdong, 510280, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：