دورية أكاديمية
Discovery of Biaryl Amide Derivatives as Potent, Selective, and Orally Bioavailable RORγt Agonists for Cancer Immunotherapy
| العنوان: | Discovery of Biaryl Amide Derivatives as Potent, Selective, and Orally Bioavailable RORγt Agonists for Cancer Immunotherapy |
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| المؤلفون: | Lixue Lu, Yafei Huang, Meiqi Song, Nannan Sun, Li Xia, Mingcheng Yu, Meiling Zhao, Ruomeng Qiu, Ji-an Chen, Yunpeng Zhao, Haojie Wang, Huimin Guo, Yan Li, Di Zhu, Yonghui Wang, Qiong Xie |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biochemistry, Cell Biology, Genetics, Molecular Biology, Pharmacology, Biotechnology, Immunology, Cancer, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, sup >+, preclinical tumor models, mouse b16f10 melanoma, llc lung adenocarcinoma, demonstrated robust efficacy, current studies indicate, biaryl amide derivatives, rorγt agonists provide, novel rorγt agonists, 14 , vivo <, taken together, reachable approach, pharmacokinetic profiles, cancer immunotherapy |
| الوصف: | The master transcription factor receptor retinoic acid receptor-related orphan receptor γt (RORγt) regulates the differentiation of T-helper 17 (Th17) cells and the production of interleukin-17 (IL-17). Activation of RORγt + T cells in the tumor microenvironment promotes immune infiltration to more effectively inhibit tumor growth. Therefore, RORγt agonists provide a reachable approach to cancer immunotherapy. Herein, a series of biaryl amide derivatives as novel RORγt agonists were designed, synthesized, and evaluated. Starting from the reported RORγt inverse agonist GSK805 ( 1 ), “functionality switching” and structure-based drug optimization led to the discovery of a promising RORγt agonist lead compound 14 , which displayed potent and selective RORγt agonist activity and significantly improved metabolic stability. With excellent in vivo pharmacokinetic profiles, compound 14 demonstrated robust efficacy in preclinical tumor models of mouse B16F10 melanoma and LLC lung adenocarcinoma. Taken together, current studies indicate that 14 deserves further investigation as a potential lead RORγt agonist for cancer immunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Discovery_of_Biaryl_Amide_Derivatives_as_Potent_Selective_and_Orally_Bioavailable_ROR_t_Agonists_for_Cancer_Immunotherapy/24591888Test |
| DOI: | 10.1021/acs.jmedchem.3c01492.s001 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.3c01492.s001Test https://figshare.com/articles/journal_contribution/Discovery_of_Biaryl_Amide_Derivatives_as_Potent_Selective_and_Orally_Bioavailable_ROR_t_Agonists_for_Cancer_Immunotherapy/24591888Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.51FA42D1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.3c01492.s001 |
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