A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

Redox Biology - Tập 34 - Trang 101565 - 2020
Mengchen Lu1,2, Xian Zhang1, Jing Zhao1, Qidong You1,2, Zhengyu Jiang1,2
1State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
2Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Tài liệu tham khảo

Tebay, 2015, Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease, Free Radic. Biol. Med., 88, 108, 10.1016/j.freeradbiomed.2015.06.021 Tonelli, 2018, Transcriptional regulation by Nrf2, Antioxidants Redox Signal., 29, 1727, 10.1089/ars.2017.7342 Cuadrado, 2018, Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach, Pharmacol. Rev., 70, 348, 10.1124/pr.117.014753 Suzuki, 2017, Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress, J. Biol. Chem., 292, 16817, 10.1074/jbc.R117.800169 Abed, 2015, Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents, Acta Pharm. Sin. B, 5, 285, 10.1016/j.apsb.2015.05.008 Lu, 2016, The keap1–Nrf2–ARE pathway as a potential preventive and therapeutic target: an update, Med. Res. Rev., 36, 924, 10.1002/med.21396 Yamamoto, 2018, The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis, Physiol. Rev., 98, 1169, 10.1152/physrev.00023.2017 Keleku-Lukwete, 2018, An overview of the advantages of KEAP1-NRF2 system activation during inflammatory disease treatment, Antioxidants Redox Signal., 29, 1746, 10.1089/ars.2017.7358 Cuadrado, 2019, Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases, Nat. Rev. Drug Discov., 18, 295, 10.1038/s41573-018-0008-x Zhou, 2020, Recent progress in the development of small molecule Nrf2 activators: a patent review (2017-present), Expert Opin. Ther. Pat., 30, 209, 10.1080/13543776.2020.1715365 Davies, 2016, Monoacidic inhibitors of the kelch-like ECH-associated protein 1: nuclear factor erythroid 2-related factor 2 (KEAP1:NRF2) protein–protein interaction with high cell potency identified by fragment-based discovery, J. Med. Chem., 59, 3991, 10.1021/acs.jmedchem.6b00228 Heightman, 2019, Structure-activity and structure-conformation relationships of aryl propionic acid inhibitors of the kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (KEAP1/NRF2) protein-protein interaction, J. Med. Chem., 62, 4683, 10.1021/acs.jmedchem.9b00279 Lazzara, 2019, Isoquinoline kelch-like ECH-associated protein 1-nuclear factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) inhibitors with high metabolic stability, J. Med. Chem. Jiang, 2018, Identification of a novel small-molecule Keap1-Nrf2 PPI inhibitor with cytoprotective effects on LPS-induced cardiomyopathy, J. Enzym. Inhib. Med. Chem., 33, 833, 10.1080/14756366.2018.1461856 Ma, 2020, Design, synthesis and identification of novel, orally bioavailable non-covalent Nrf2 activators, Bioorg. Med. Chem. Lett, 30, 126852, 10.1016/j.bmcl.2019.126852 Abed, 2020, Discovery of disubstituted xylylene derivatives as small molecule direct inhibitors of Keap1-Nrf2 protein-protein interaction, Bioorg. Med. Chem., 28, 115343, 10.1016/j.bmc.2020.115343 Meng, 2018, Fragment-growing guided design of Keap1-Nrf2 protein-protein interaction inhibitors for targeting myocarditis, Free Radic. Biol. Med., 117, 228, 10.1016/j.freeradbiomed.2018.02.010 Jiang, 2016, Discovery and development of kelch-like ECH-associated protein 1: nuclear factor erythroid 2-related factor 2 (KEAP1:NRF2) protein-protein interaction inhibitors: achievements, challenges and future directions, J. Med. Chem., 59, 10837, 10.1021/acs.jmedchem.6b00586 Pallesen, 2018, Non-covalent small-molecule kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) inhibitors and their potential for targeting central nervous system diseases, J. Med. Chem., 61, 8088, 10.1021/acs.jmedchem.8b00358 Zhuang, 2017, Small molecules inhibiting Keap1-Nrf2 protein-protein interactions: a novel approach to activate Nrf2 function, MedChemComm, 8, 286, 10.1039/C6MD00500D DeNicola, 2011, Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis, Nature, 475, 106, 10.1038/nature10189 Lignitto, 2019, Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1, Cell, 178, 316, 10.1016/j.cell.2019.06.003 Jiang, 2019, Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition: an emerging strategy in cancer therapy, J. Med. Chem., 62, 3840, 10.1021/acs.jmedchem.8b01121 Rojo de la Vega, 2018, NRF2 and the hallmarks of cancer, Canc. Cell, 34, 21, 10.1016/j.ccell.2018.03.022 Robledinos-Anton, 2019, Activators and inhibitors of NRF2: a review of their potential for clinical development, Oxid. Med. Cell. Longev., 2019, 9372182, 10.1155/2019/9372182 Menegon, 2016, The dual roles of NRF2 in cancer, Trends Mol. Med., 22, 578, 10.1016/j.molmed.2016.05.002 Zavattari, 2015, Nrf2, but not beta-catenin, mutation represents an early event in rat hepatocarcinogenesis, Hepatology, 62, 851, 10.1002/hep.27790 Orru, 2018, Genetic inactivation of Nrf2 prevents clonal expansion of initiated cells in a nutritional model of rat hepatocarcinogenesis, J. Hepatol., 69, 635, 10.1016/j.jhep.2018.05.010 Stone, 2006, Hydrogen peroxide: a signaling messenger, Antioxidants Redox Signal., 8, 243, 10.1089/ars.2006.8.243 Radi, 2018, Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine, Proc. Natl. Acad. Sci. U. S. A, 115, 5839, 10.1073/pnas.1804932115 Sies, 2017, Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress, Redox Biol., 11, 613, 10.1016/j.redox.2016.12.035 D'Autreaux, 2007, ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis, Nat. Rev. Mol. Cell Biol., 8, 813, 10.1038/nrm2256 Veal, 2007, Hydrogen peroxide sensing and signaling, Mol. Cell, 26, 1, 10.1016/j.molcel.2007.03.016 Mittal, 2014, Reactive oxygen species in inflammation and tissue injury, Antioxidants Redox Signal., 20, 1126, 10.1089/ars.2012.5149 Barnham, 2004, Neurodegenerative diseases and oxidative stress, Nat. Rev. Drug Discov., 3, 205, 10.1038/nrd1330 Reuter, 2010, Oxidative stress, inflammation, and cancer: how are they linked?, Free Radic. Biol. Med., 49, 1603, 10.1016/j.freeradbiomed.2010.09.006 Weinstain, 2014, In vivo targeting of hydrogen peroxide by activatable cell-penetrating peptides, J. Am. Chem. Soc., 136, 874, 10.1021/ja411547j Chang, 2004, A selective, cell-permeable optical probe for hydrogen peroxide in living cells, J. Am. Chem. Soc., 126, 15392, 10.1021/ja0441716 Miller, 2005, Boronate-based fluorescent probes for imaging cellular hydrogen peroxide, J. Am. Chem. Soc., 127, 16652, 10.1021/ja054474f Van de Bittner, 2010, In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter, Proc. Natl. Acad. Sci. U. S. A, 107, 21316, 10.1073/pnas.1012864107 Dickinson, 2011, Chemistry and biology of reactive oxygen species in signaling or stress responses, Nat. Chem. Biol., 7, 504, 10.1038/nchembio.607 Hagen, 2012, Aminoferrocene-based prodrugs activated by reactive oxygen species, J. Med. Chem., 55, 924, 10.1021/jm2014937 Yuan, 2012, Single fluorescent probe responds to H2O2, NO, and H2O2/NO with three different sets of fluorescence signals, J. Am. Chem. Soc., 134, 1305, 10.1021/ja2100577 Kolanowski, 2016, Selective and reversible approaches toward imaging redox signaling using small-molecule probes, Antioxidants Redox Signal., 24, 713, 10.1089/ars.2015.6588 Wu, 2019, Reaction-based fluorescent probes for the detection and imaging of reactive oxygen, nitrogen, and sulfur species, Acc. Chem. Res., 52, 2582, 10.1021/acs.accounts.9b00302 Kuang, 2011, Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs, J. Am. Chem. Soc., 133, 19278, 10.1021/ja2073824 Kim, 2014, An activatable prodrug for the treatment of metastatic tumors, J. Am. Chem. Soc., 136, 13888, 10.1021/ja5077684 Daum, 2015, Improved synthesis of N-benzylaminoferrocene-based prodrugs and evaluation of their toxicity and antileukemic activity, J. Med. Chem., 58, 2015, 10.1021/jm5019548 Daum, 2017, Lysosome-targeting amplifiers of reactive oxygen species as anticancer prodrugs, Angew. Chem., Int. Ed. Engl., 56, 15545, 10.1002/anie.201706585 Chen, 2018, Discovery and optimization of novel hydrogen peroxide activated aromatic nitrogen mustard derivatives as highly potent anticancer agents, J. Med. Chem., 61, 9132, 10.1021/acs.jmedchem.8b00559 Reshetnikov, 2018, ROS-responsive N-alkylaminoferrocenes for cancer-cell-specific targeting of mitochondria, Angew. Chem., Int. Ed. Engl., 57, 11943, 10.1002/anie.201805955 Wang, 2019, Enhanced antitumor efficacy by a cascade of reactive oxygen species generation and drug release, Angew. Chem., Int. Ed. Engl., 58, 14758, 10.1002/anie.201908997 Meng, 2019, Introduction of the α-ketoamide structure: en route to develop hydrogen peroxide responsive prodrugs, Chem. Sci., 10, 7156, 10.1039/C9SC00910H Peiro Cadahia, 2018, Synthesis and evaluation of hydrogen peroxide sensitive prodrugs of methotrexate and aminopterin for the treatment of rheumatoid arthritis, J. Med. Chem., 61, 3503, 10.1021/acs.jmedchem.7b01775 Andersen, 2018, Methotrexate prodrugs sensitive to reactive oxygen species for the improved treatment of rheumatoid arthritis, Eur. J. Med. Chem., 156, 738, 10.1016/j.ejmech.2018.07.045 Zhao, 2019, Fluorogenic hydrogen sulfide (H2S) donors based on sulfenyl thiocarbonates enable H2S tracking and quantification, Chem. Sci., 10, 1873, 10.1039/C8SC05200J Zhao, 2016, Hydrogen sulfide donors activated by reactive oxygen species, Angew. Chem. Int. Ed., 55, 14638, 10.1002/anie.201608052 Li, 2018, A two-photon H2 O2 -activated CO photoreleaser, Angew. Chem., Int. Ed. Engl., 57, 12415, 10.1002/anie.201805806 Hoang, 2017, A boronic acid conjugate of angiogenin that shows ROS-responsive neuroprotective activity, Angew. Chem., 129, 2663, 10.1002/ange.201611446 Jiang, 2015, Structure-activity and structure-property relationship and exploratory in vivo evaluation of the nanomolar keap1-Nrf2 protein-protein interaction inhibitor, J. Med. Chem., 58, 6410, 10.1021/acs.jmedchem.5b00185 Jiang, 2014, Discovery of potent keap1–Nrf2 protein–protein interaction inhibitor based on molecular binding determinants analysis, J. Med. Chem., 57, 2736, 10.1021/jm5000529 Jain, 2015, Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators, Eur. J. Med. Chem., 103, 252, 10.1016/j.ejmech.2015.08.049 Tran, 2019, A comparative assessment study of known small-molecule keap1-Nrf2 protein-protein interaction inhibitors: chemical synthesis, binding properties, and cellular activity, J. Med. Chem., 62, 8028, 10.1021/acs.jmedchem.9b00723 Lu, 2019, CPUY192018, a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, alleviates renal inflammation in mice by restricting oxidative stress and NF-kappaB activation, Redox Biol., 26, 101266, 10.1016/j.redox.2019.101266 Perez, 2015, Exploring hydrogen peroxide responsive thiazolidinone-based prodrugs, Chem. Commun., 51, 7116, 10.1039/C4CC09921D Kobayashi, 2016, Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription, Nat. Commun., 7, 11624, 10.1038/ncomms11624 Mukhopadhyay, 2020, Undermining glutaminolysis bolsters chemotherapy while NRF2 promotes chemoresistance in KRAS-driven pancreatic cancers, Canc. Res., 80, 1630, 10.1158/0008-5472.CAN-19-1363 Bailey, 2018, Comprehensive characterization of cancer driver genes and mutations, Cell, 173, 371, 10.1016/j.cell.2018.02.060 Cloer, 2019, NRF2 activation in cancer: from DNA to protein, Canc. Res., 79, 889, 10.1158/0008-5472.CAN-18-2723 Lignitto, 2019, Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1, Cell, 178, 316, 10.1016/j.cell.2019.06.003 Zhang, 2020, Emerging substrate proteins of kelch-like ECH associated protein 1 (Keap1) and potential challenges for the development of small-molecule inhibitors of the keap1-nuclear factor erythroid 2-related factor 2 (Nrf2) protein-protein interaction, J. Med. Chem., 10.1021/acs.jmedchem.9b01865 Kopacz, 2020, Beyond repression of Nrf2: an update on Keap1, Free Radical Biol. Med., 10.1016/j.freeradbiomed.2020.03.023