| Autor: |
Peiran Song, Gang Bai, Shingpan Chan, Tao Zhang, Linjiang Tong, Yi Su, Yanyan Shen, Yi Chen, Yingqiang Liu, Mengzhen Lai, Yi Ning, Haotian Tang, Yan Fang, Ke Ding, Jian Ding, Hua Xie |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Frontiers in Pharmacology, Vol 13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1663-9812 |
| DOI: |
10.3389/fphar.2022.1071114 |
| Popis: |
Hyperactivation of Bruton’s tyrosine kinase (BTK) or interleukin-2-inducible T cell kinase (ITK) has been attributed to the pathogenesis of B-cell lymphoma or T-cell leukemia, respectively, which suggests that Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase are critical targets for the treatment of hematological malignancies. We identified a novel third-generation epidermal growth factor receptor (EGFR) inhibitor, ASK120067 (limertinib) in our previous research, which has been applied as a new drug application against non-small cell lung cancer in China. In this work, we found that ASK120067 displayed potent in vitro inhibitory efficacy against Bruton’s tyrosine kinase protein and interleukin-2-inducible T cell kinase protein via covalent binding. In cell-based assays, ASK120067 dose-dependently suppressed Bruton’s tyrosine kinase phosphorylation and exhibited anti-proliferation potency by inducing apoptosis in numerous B-lymphoma cells. Meanwhile, it caused growth arrest and induced the apoptosis of T-cell leukemia cells by attenuating interleukin-2-inducible T cell kinase activation. Oral administration of ASK120067 led to significant tumor regression in B-cell lymphoma and T-cell leukemia xenograft models by weakening Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase signaling, respectively. Taken together, our studies demonstrated that ASK120067 exerted preclinical anti-tumor activities against B-/T-cell malignancy by targeting BTK/ITK. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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