用于局部抑制TLR4诱导炎症的Tak-242前药的设计与催化活化
Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation.
作者信息
Plunk Michael A, Alaniz Alyssa, Olademehin Olatunde P, Ellington Thomas L, Shuford Kevin L, Kane Robert R
机构信息
Department of Chemistry and Biochemistry, Baylor University, Waco, Texas 76798, United States.
Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States.
出版信息
ACS Med Chem Lett. 2020 Jan 3;11(2):141-146. doi: 10.1021/acsmedchemlett.9b00518. eCollection 2020 Feb 13.
Abstract
Tak-242 (resatorvid), a Toll-like Receptor 4 (TLR4) inhibitor, has been identified as a potent suppressor of innate inflammation. As a strategy to target Tak-242 to select tissue, four TLR4-inactive prodrugs were synthesized for activation via two different release mechanisms. Two nitrobenzyl Tak-242 prodrugs released the parent drug upon exposure to the exogenous enzyme nitroreductase, while the two propargyl prodrugs were converted to Tak-242 in the presence of Pd.
摘要
Tak-242（瑞斯托维德）是一种Toll样受体4（TLR4）抑制剂，已被确定为先天性炎症的有效抑制剂。作为将Tak-242靶向特定组织的策略，合成了四种TLR4无活性前药，通过两种不同的释放机制进行激活。两种硝基苄基Tak-242前药在暴露于外源性酶硝基还原酶时释放母体药物，而两种炔丙基前药在钯存在下转化为Tak-242。
相似文献
1
Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation.用于局部抑制TLR4诱导炎症的Tak-242前药的设计与催化活化
ACS Med Chem Lett. 2020 Jan 3;11(2):141-146. doi: 10.1021/acsmedchemlett.9b00518. eCollection 2020 Feb 13.
2
Design and Catalyzed Activation of Mycophenolic Acid Prodrugs.霉酚酸前药的设计与催化活化
ACS Med Chem Lett. 2021 Apr 8;12(5):812-816. doi: 10.1021/acsmedchemlett.1c00079. eCollection 2021 May 13.
3
Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: new insight into the anticancer effect of TAK-242 (Resatorvid).TLR4 的小分子抑制剂抑制卵巢癌细胞增殖：TAK-242（Resatorvid）抗癌作用的新见解。
Cancer Chemother Pharmacol. 2020 Jan;85(1):47-59. doi: 10.1007/s00280-019-03988-y. Epub 2019 Nov 30.
4
TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules.TAK-242（resatorvid）是一种小分子 Toll 样受体（TLR）4 信号通路抑制剂，能选择性地与 TLR4 结合，并干扰 TLR4 与其衔接分子之间的相互作用。
Mol Pharmacol. 2011 Jan;79(1):34-41. doi: 10.1124/mol.110.068064. Epub 2010 Sep 29.
5
Sulfonamide Prodrugs with a Two-Stage Release Mechanism for the Efficient Delivery of the TLR4 Antagonist TAK-242.具有两阶段释放机制的磺胺前药，用于高效递送TLR4拮抗剂TAK-242。
ACS Med Chem Lett. 2022 Dec 9;14(1):110-115. doi: 10.1021/acsmedchemlett.2c00492. eCollection 2023 Jan 12.
6
Blockade of TLR4 using TAK-242 (resatorvid) enhances anti-cancer effects of chemotherapeutic agents: a novel synergistic approach for breast and ovarian cancers.使用 TAK-242（resatorvid）阻断 TLR4 增强化疗药物的抗癌作用：乳腺癌和卵巢癌的一种新协同方法。
Immunol Res. 2019 Dec;67(6):505-516. doi: 10.1007/s12026-019-09113-8.
7
Toll-like receptor 4 inhibitor protects against retinal ganglion cell damage induced by optic nerve crush in mice.Toll样受体4抑制剂可保护小鼠免受视神经挤压诱导的视网膜神经节细胞损伤。
J Pharmacol Sci. 2017 Mar;133(3):176-183. doi: 10.1016/j.jphs.2017.02.012. Epub 2017 Mar 2.
8
Toll-like receptor 4 inhibitor TAK-242 treatment does not influence perfusion recovery in tissue ischemia.Toll 样受体 4 抑制剂 TAK-242 治疗并不影响组织缺血中的灌注恢复。
J Cardiovasc Pharmacol. 2014 Jan;63(1):16-22. doi: 10.1097/FJC.0000000000000019.
9
Nanoparticle incorporating Toll-like receptor 4 inhibitor attenuates myocardial ischaemia-reperfusion injury by inhibiting monocyte-mediated inflammation in mice.纳米颗粒包裹 Toll 样受体 4 抑制剂通过抑制单核细胞介导致炎减轻小鼠心肌缺血再灌注损伤。
Cardiovasc Res. 2019 Jun 1;115(7):1244-1255. doi: 10.1093/cvr/cvz066.
10
Toll-Like Receptor-4 Inhibitor TAK-242 Attenuates Motor Dysfunction and Spinal Cord Pathology in an Amyotrophic Lateral Sclerosis Mouse Model.Toll样受体4抑制剂TAK-242减轻肌萎缩侧索硬化小鼠模型中的运动功能障碍和脊髓病理变化。
Int J Mol Sci. 2017 Aug 1;18(8):1666. doi: 10.3390/ijms18081666.
引用本文的文献
1
Insights into the gut-liver axis: mechanisms and emerging therapies in hepatocellular carcinoma.洞悉肠-肝轴：肝细胞癌的机制与新兴疗法
Front Pharmacol. 2025 May 19;16:1595853. doi: 10.3389/fphar.2025.1595853. eCollection 2025.
2
Co-inhibition of RAGE and TLR4 sensitizes pancreatic cancer to irreversible electroporation in mice by disrupting autophagy.RAGE和TLR4的共同抑制通过破坏自噬使小鼠胰腺癌对不可逆电穿孔敏感。
Acta Pharmacol Sin. 2025 Jun;46(6):1757-1771. doi: 10.1038/s41401-025-01487-w. Epub 2025 Feb 14.
3
Resatorvid (TAK-242) Ameliorates Ulcerative Colitis by Modulating Macrophage Polarization and T Helper Cell Balance via TLR4/JAK2/STAT3 Signaling Pathway.Resatorvid（TAK-242）通过 TLR4/JAK2/STAT3 信号通路调节巨噬细胞极化和辅助性 T 细胞平衡改善溃疡性结肠炎。
Inflammation. 2024 Dec;47(6):2108-2128. doi: 10.1007/s10753-024-02028-z. Epub 2024 May 18.
4
Development of Biocompatible Cu(I)-Microdevices for Bioorthogonal Uncaging and Click Reactions.用于生物正交解笼和点击反应的生物相容 Cu(I)-微器件的开发。
Chemistry. 2024 May 28;30(30):e202400611. doi: 10.1002/chem.202400611. Epub 2024 Apr 16.
5
Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics.真正具有生物相容性的金催化实现了抗焦虑药物在中枢神经系统内的体内正交释放。
Angew Chem Weinheim Bergstr Ger. 2022 Jan 3;134(1):e202111461. doi: 10.1002/ange.202111461. Epub 2021 Nov 18.
6
A narrative review: progress in transition metal-mediated bioorthogonal catalysis for the treatment of solid tumors.一篇叙述性综述：过渡金属介导的生物正交催化在实体瘤治疗中的进展
Transl Cancer Res. 2023 Aug 31;12(8):2181-2196. doi: 10.21037/tcr-23-345. Epub 2023 Aug 28.
7
Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review).NLRP3 炎性小体通路抑制剂作为炎症性疾病有希望的治疗候选物（综述）。
Int J Mol Med. 2023 Apr;51(4). doi: 10.3892/ijmm.2023.5238. Epub 2023 Mar 24.
8
Dual-Bioorthogonal Catalysis by a Palladium Peptide Complex.钯肽配合物的双生物正交催化。
J Med Chem. 2023 Mar 9;66(5):3301-3311. doi: 10.1021/acs.jmedchem.2c01689. Epub 2023 Feb 23.
9
Sulfonamide Prodrugs with a Two-Stage Release Mechanism for the Efficient Delivery of the TLR4 Antagonist TAK-242.具有两阶段释放机制的磺胺前药，用于高效递送TLR4拮抗剂TAK-242。
ACS Med Chem Lett. 2022 Dec 9;14(1):110-115. doi: 10.1021/acsmedchemlett.2c00492. eCollection 2023 Jan 12.
10
Bioorthogonal Catalysis by Encapsulated Nanoalloys: Overcoming Intracellular Deactivation.纳米合金的生物正交催化：克服细胞内失活。
Nano Lett. 2023 Feb 8;23(3):804-811. doi: 10.1021/acs.nanolett.2c03593. Epub 2023 Jan 17.
本文引用的文献
1
Bright insights into palladium-triggered local chemotherapy.钯触发局部化疗的深刻见解。
Chem Sci. 2018 Jul 17;9(37):7354-7361. doi: 10.1039/c8sc02291g. eCollection 2018 Oct 7.
2
Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium-Functionalized Microdevices.钯功能化微器件对伊立替康活性代谢物的生物正交去笼。
Chemistry. 2018 Nov 13;24(63):16783-16790. doi: 10.1002/chem.201803725. Epub 2018 Nov 8.
3
Early TLR4 Blockade Attenuates Sterile Inflammation-mediated Stress in Islets During Isolation and Promotes Successful Transplant Outcomes.早期 TLR4 阻断可减轻胰岛分离过程中无菌性炎症介导的应激，促进移植成功。
Transplantation. 2018 Sep;102(9):1505-1513. doi: 10.1097/TP.0000000000002287.
4
The expanding role of prodrugs in contemporary drug design and development.前药在当代药物设计和开发中的作用不断扩大。
Nat Rev Drug Discov. 2018 Aug;17(8):559-587. doi: 10.1038/nrd.2018.46. Epub 2018 Apr 27.
5
Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation.离体生成载药胰岛通过抑制 TLR4 介导的 NFkB 上调改善移植效果。
Biomaterials. 2018 Mar;159:13-24. doi: 10.1016/j.biomaterials.2017.12.020. Epub 2017 Dec 28.
6
Targeted antitumor therapy mediated by prodrug-activating mesenchymal stromal cells.靶向肿瘤治疗的前药激活间充质基质细胞。
Cancer Lett. 2017 Nov 1;408:1-9. doi: 10.1016/j.canlet.2017.08.016. Epub 2017 Aug 25.
7
Gold-Triggered Uncaging Chemistry in Living Systems.活体系统中的金触发解笼化学。
Angew Chem Int Ed Engl. 2017 Oct 2;56(41):12548-12552. doi: 10.1002/anie.201705609. Epub 2017 Aug 9.
8
Prodrugs in medicinal chemistry and enzyme prodrug therapies.前药在药物化学和酶前药疗法中的应用。
Adv Drug Deliv Rev. 2017 Sep 1;118:65-77. doi: 10.1016/j.addr.2017.06.013. Epub 2017 Jul 1.
9
A two-photon fluorescent probe for nitroreductase imaging in living cells, tissues and zebrafish under hypoxia conditions.一种双光子荧光探针，用于在缺氧条件下活细胞、组织和斑马鱼中的硝基还原酶成像。
Analyst. 2017 May 2;142(9):1545-1553. doi: 10.1039/c7an00058h.
10
Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor.高效钯触发的生物正交前药伏立诺他释放。
J Med Chem. 2016 Nov 10;59(21):9974-9980. doi: 10.1021/acs.jmedchem.6b01426. Epub 2016 Nov 2.
Zotero 插件