Article
Chemistry, Medicinal
Haixia Liu, Xinyu Ding, Linyi Liu, Qianglong Mi, Quanju Zhao, Yubao Shao, Chaowei Ren, Jinju Chen, Ying Kong, Xing Qiu, Nicola Elvassore, Xiaobao Yang, Qianqian Yin, Biao Jiang
Summary: Protein degradation through CRBN-recruiting PROTACs has shown promising potential in targeting oncogenic fusion protein BCR-ABL, providing a potential therapeutic strategy for chronic myeloid leukemia.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Bohan Ma, Hui Feng, Chao Feng, Yi Liu, Hailing Zhang, Jincheng Wang, Wenjuan Wang, Pengcheng He, Fan Niu
Summary: The study designed a dual-targeting proteolysis-targeting chimera (PROTAC) type drug that can induce Bcr/Abl degradation and activate the p53 pathway simultaneously, potentially overcoming drug resistance in Ph+ leukemias.
Article
Pharmacology & Pharmacy
Tingting Lu, Jiangyan Cao, Fengming Zou, Xixiang Li, Aoli Wang, Wenliang Wang, Huamin Liang, Qingwang Liu, Chen Hu, Cheng Chen, Zhenquan Hu, Wenchao Wang, Lili Li, Jian Ge, Yang Shen, Tao Ren, Jing Liu, Ruixiang Xia, Qingsong Liu
Summary: CHMFL-48 is a novel type II kinase inhibitor that potently inhibits the wild-type BCR-ABL kinase and a panel of imatinib-resistant mutants. This drug shows strong inhibitory activity in a cellular context, blocking autophosphorylation of BCR-ABL kinase, affecting downstream signaling mediators, and inducing cell cycle progression blockade and apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ashraf K. El-Damasy, Heewon Jin, Jung Woo Park, Hyun Ji Kim, Hanan Khojah, Seon Hee Seo, Ju-Hyeon Lee, Eun-Kyoung Bang, Gyochang Keum
Summary: This study identifies AK-HW-90 (2b) as a potent inhibitor against imatinib-resistant BCR-ABL mutants, especially T315I. AK-HW-90 exhibits superior anticancer activity compared to imatinib and shows strong cytotoxicity against multiple cancer cells, including leukemia cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Liling Jiang, Qingyan He, Xin Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Xinmei Chen, Huan Zhou, Yi Meng, Bingyuan Liu, Guanjie Peng, Chunyan Wang, Jinbao Liu, Xianping Shi
Summary: This study found that the proteasomal deubiquitinases USP14 and UCHL5 were overexpressed in primary cancer cells from CML patients. The inhibitor of USP14 and UCHL5, b-AP15, displayed potent tumor-killing activity in BCR-ABL(WT) and BCR-ABL(T315I) CML cell lines, as well as in CML xenografts and primary CML cells. Inhibition of USP14 and UCHL5, either pharmacologically or genetically, induced cell apoptosis and decreased the protein level of BCR-ABL in CML cells expressing BCR-ABL(WT) and BCR-ABL(T315I). Moreover, b-AP15 synergistically enhanced the cytotoxic effect of TKI imatinib in BCR-ABL(WT) and BCR-ABL(T315I) CML cells.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
You-lu Pan, Shen-xin Zeng, Rong-rong Hao, Mei-hao Liang, Zheng-rong Shen, Wen-hai Huang
Summary: This review summarizes the current research progress of inhibitors and degraders targeting BCR-ABL for the treatment of CML, including first, second, and third-generation tyrosine kinase inhibitors targeting different mutations, as well as allosteric inhibitors and proteolysis-targeting chimeras (PROTAC) based on different E3 ligands.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Dachuan Zeng, Miao Gao, Renren Zheng, Run Qin, Wei He, Suotian Liu, Wei Wei, Zhenglan Huang
Summary: The study revealed that KW-2478 has anti-cancer properties in both imatinib-sensitive and imatinib-resistant CML cells by inhibiting the chaperone function of HSP90α, weakening the BCR/ABL and MAPK signaling pathways. In mouse models, KW-2478 effectively prolonged lifespan and alleviated disease symptoms.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Yun Xu, Ziting Wang, Lei Zhang, Congying Gao, Fahui Li, Xueming Li, Yu Ke, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The compound JOA can inhibit the proliferation of chronic myeloid leukemia cells, including those with the BCR-ABL-T315I mutation, and induce cell differentiation. This effect may be mediated by the inhibition of the BCR-ABL/c-MYC signaling pathway. JOA shows potential as a lead compound for overcoming imatinib resistance in CML therapy.
Article
Chemistry, Multidisciplinary
Rodrigo A. Gama-Brambila, Jie Chen, Yasamin Dabiri, Georg Tascher, Vaclav Nemec, Christian Muench, Guangqi Song, Stefan Knapp, Xinlai Cheng
Summary: The discovery of clustered regularly interspaced short palindromic repeats and their associated proteins has led to the development of new methods to control Cas proteins, including fusion proteins and PROTACs. Engineering Cas proteins with a pi-clamp system allows for labeling and degradation in live cells, showing a wide range of potential applications in regulating stability and activity of FCPF-tagging proteins through perfluoroaromatics-induced proximity.
Article
Multidisciplinary Sciences
Hu Lei, Han-Zhang Xu, Hui-Zhuang Shan, Meng Liu, Ying Lu, Zhi-Xiao Fang, Jin Jin, Bo Jing, Xin-Hua Xiao, Shen-Meng Gao, Feng-Hou Gao, Li Xia, Li Yang, Li-Gen Liu, Wei-Wei Wang, Chuan-Xu Liu, Yin Tong, Yun-Zhao Wu, Jun-Ke Zheng, Guo-Qiang Chen, Li Zhou, Ying-Li Wu
Summary: This study reveals that targeting the ubiquitin peptidase USP47 can overcome TKI resistance and eliminate leukemia stem/progenitor cells in CML.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Zhen Liu, Wenlong Zheng, Yuan Liu, Binghe Zhou, Yuqing Zhang, Fan Wang
Summary: The study showed that HSPA8 is overexpressed in imatinib-resistant CML cells and its ablation can inhibit cell proliferation, induce autophagy, and enhance the anti-tumor activity of imatinib. These findings reveal the role of HSPA8 in IR-CML and suggest its potential as a target for treatment.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Oncology
Priyanka Singh
Summary: This study identified 111 miRNAs that potentially target the PI3K/Akt/mTOR pathway, and selected seven miRNAs for further investigation. Except for hsa-miR-199a-3p, the other six miRNAs have been extensively studied in AML. Given the similarity between AML and CML, these miRNAs may also be advantageous for treating chemoresistance in CML.
Article
Oncology
Shailaja Hegde, Anjelika Gasilina, Mark Wunderlich, Yuan Lin, Marcel Buchholzer, Oliver H. F. Krumbach, Mohammad Akbarzadeh, Mohammad Reza Ahmadian, William Seibel, Yi Zheng, John P. Perentesis, Benjamin E. Mizukawa, Lisa Privette Vinnedge, Jose A. Cancelas, Nicolas N. Nassar
Summary: The small-molecule inhibitor IODVA1 targeting VAV3 effectively inhibits RAC activation and signaling, leading to increased pro-apoptotic activity in BCR-ABL1-transformed cells. In difficult-to-treat pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models, IODVA1 outperforms dasatinib or ponatinib and provides a more durable response after treatment withdrawal.
Article
Oncology
Nilgun Karasu, Hilal Akalin, Nuriye Gokce, Abdulbaki Yildirim, Mikail Demir, Hande Kulak, Serhat Celik, Muzaffer Keklik, Munis Dundar
Summary: Pyrosequencing detected a certain proportion of BCR/ABL mutations in patients with chronic myeloid leukemia, with a higher positive rate in patients who had no response to imatinib treatment. Performing NGS analysis on patients resistant to imatinib helps identify more mutations.