دورية أكاديمية

CJ 2 : A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

التفاصيل البيبلوغرافية
العنوان: CJ 2 : A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane
المؤلفون: Renming Fan (14321495), Aohua Deng (14321498), Bing Qi (492962), Shuo Zhang (30844), Ruoxi Sang (14321501), Lanxin Luo (5868185), Jiakui Gou (14321504), Yongqing Liu (17191), Ruizhuo Lin (14321507), Minggao Zhao (14258060), Yang Liu (4829), Le Yang (345935), Maosheng Cheng (1409932), Gaofei Wei (7436060)
سنة النشر: 2023
مصطلحات موضوعية: Biochemistry, Molecular Biology, Pharmacology, Biotechnology, Immunology, Mental Health, Space Science, Chemical Sciences not elsewhere classified, various cancer patients, sup >+, prodrug enhances chemo, enhancing dna damage, primary chemotherapy drugs, novel potent platinum, elevated immune response, potent therapeutic activity, could accelerate pd, cytomembrane platinum drugs, platinum drugs, immune response, therapeutic applicability, synthesized platinum, could arouse, immune system, side effects, promote cd8, limited due, ligand jq, less toxicity, l1 synthesis
الوصف: Platinum drugs as primary chemotherapy drugs have been applied to various cancer patients. However, their therapeutic applicability is limited due to the adverse effects and immunosuppression. To minimize the side effects and boost the immune response, we designed and synthesized platinum(IV) prodrugs that introduced BRD4 inhibitor JQ-1. Among them, CJ 2 had the most potent therapeutic activity and less toxicity. With the introduction of ligand JQ-1, CJ 2 -reduced PD-L1 protein was found in the cytoplasm and cytomembrane for the first time. By interfering with the PD-L1 synthesis, CJ 2 could arouse the immune system and promote CD8 + T cell infiltration. Meanwhile, CJ 2 could accelerate PD-L1 degradation in the cytoplasm to block DNA damage repair. In vivo, CJ 2 markedly suppressed tumor growth by reversing the immunosuppression microenvironment and enhancing DNA damage. These findings provide an effective approach to improve the selectivity and activity of the platinum drugs with elevated immune response.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
العلاقة: https://figshare.com/articles/journal_contribution/_b_CJ_b_sub_b_2_b_sub_A_Novel_Potent_Platinum_IV_Prodrug_Enhances_Chemo-Immunotherapy_by_Facilitating_PD-L1_Degradation_in_the_Cytoplasm_and_Cytomembrane/21806636Test
DOI: 10.1021/acs.jmedchem.2c01719.s001
الإتاحة: https://doi.org/10.1021/acs.jmedchem.2c01719.s001Test
حقوق: CC BY-NC 4.0
رقم الانضمام: edsbas.8887E44
قاعدة البيانات: BASE