التفاصيل البيبلوغرافية
| العنوان: |
Repurposing Ponatinib as a PD-L1 Inhibitor Revealed by Drug Repurposing Screening and Validation by In Vitro and In Vivo Experiments |
| المؤلفون: |
Anjali Barnwal (14191305), Sanjeev Das (2692177), Jayanta Bhattacharyya (1328937) |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Medicine, Pharmacology, Biotechnology, Immunology, Cancer, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, related adverse effects, murine melanoma model, made great advances, include low permeability, high treatment costs, fluorescence quenching assay, direct toxic effect, delaying tumor growth, complex synthetic procedures, lasting antitumor responses, experiments cancer treatment, ponatinib also reduced, entirely new drug, commercially available anti, l1 inhibitor revealed, drug repurposing screening, new drug, molecule inhibitor, molecule drug, cancer cells |
| الوصف: |
Cancer treatment by inhibiting the PD-1/PD-L1 pathway using monoclonal antibodies has made great advances as it showed long-lasting antitumor responses in a wide range of cancers. However, antibodies exhibit several disadvantages, which include low permeability, immune-related adverse effects, complex synthetic procedures, and high treatment costs. Hence, small-molecule inhibitors can be used as alternatives; however, no small molecule with in vivo activity has been reported. In addition, there are many challenges in developing a new drug, including the timeline and escalating cost. Therefore, repurposing an approved drug offers advantages over the development of an entirely new drug. Herein, we identify an FDA-approved small-molecule drug, Ponatinib, as a PD-L1 inhibitor via virtual drug screening of the ZINC database. Ponatinib showed stable binding with PD-L1, with the highest binding energy among all of the screened FDA-approved drugs. The binding of Ponatinib with PD-L1 was supported by a fluorescence quenching assay and immunofluorescence study. Further, we compared the in vivo antitumor efficacy of Ponatinib with a commercially available anti-PD-L1 antibody in the murine melanoma model. Ponatinib was found to be more efficient in delaying tumor growth than the anti-PD-L1 antibody. Furthermore, Ponatinib also reduced the expression of PD-L1 in tumors and increased the T-cell population. Interestingly, splenocytes isolated from Ponatinib-treated mice showed enhanced cytotoxic T-cell (CTL) activity against B16-F10 cells. However, Ponatinib itself did not have any direct toxic effect on cancer cells in vitro . These findings suggest that Ponatinib can be used as a potent small-molecule inhibitor of PD-L1 to overcome the disadvantages associated with antibodies. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Repurposing_Ponatinib_as_a_PD-L1_Inhibitor_Revealed_by_Drug_Repurposing_Screening_and_Validation_by_i_In_Vitro_i_and_i_In_Vivo_i_Experiments/21877981 |
| DOI: |
10.1021/acsptsci.2c00214.s001 |
| الاتاحة: |
https://doi.org/10.1021/acsptsci.2c00214.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.74D8CE64 |
| قاعدة البيانات: |
BASE |