التفاصيل البيبلوغرافية
| العنوان: |
Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology |
| المؤلفون: |
Yam B. Poudel, Liqi He, Matthew Cox, Qian Zhang, Walter L. Johnson, Qiang Cong, Heng Cheng, Naidu S. Chowdari, Christine Tarby, Andrew F. Donnell, Matthais Broekema, Daniel P. O’Malley, Yong Zhang, Murugaiah A. M. Subbaiah, Boda Vijay Kumar, Lakshumanan Subramani, Bei Wang, Yi-Xin Li, Prasanna Sivaprakasam, David Critton, Dawn Mulligan, Bhupindar Sandhu, Chunshan Xie, Radha Ramakrishnan, Jignesh Nagar, Shailesh Dudhgaonkar, Martins S. Oderinde, Anwar Murtaza, Gary L. Schieven, Arvind Mathur, Ashvinikumar V. Gavai, Gregory Vite, Sanjeev Gangwar |
| سنة النشر: |
2024 |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Cell Biology, Genetics, Pharmacology, Biotechnology, Immunology, Cancer, Computational Biology, Chemical Sciences not elsewhere classified, mouse whole blood, complete tumor regression, 26 tumor model, based reporter assay, selective tlr7 agonists, novel tlr7 agonists, tlr7 agonists, developed novel, based designs, vitro <, tnfα cytokines, systemic agent, significant secretion, pharmacodynamic studies, mice showed, intravenous route |
| الوصف: |
We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro , these agonists significantly induced secretion of cytokines IL-6, IL-1β, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure–activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Discovery_of_Novel_TLR7_Agonists_as_Systemic_Agent_for_Combination_With_aPD1_for_Use_in_Immuno-oncology/24961448Test |
| DOI: |
10.1021/acsmedchemlett.3c00455.s001 |
| الإتاحة: |
https://doi.org/10.1021/acsmedchemlett.3c00455.s001Test
https://figshare.com/articles/journal_contribution/Discovery_of_Novel_TLR7_Agonists_as_Systemic_Agent_for_Combination_With_aPD1_for_Use_in_Immuno-oncology/24961448Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.1C7A313 |
| قاعدة البيانات: |
BASE |
