{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:53:34Z","timestamp":1792871614375,"version":"4.5.0"},"reference-count":146,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["R01AA029270"],"award-info":[{"award-number":["R01AA029270"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["R01AA12307"],"award-info":[{"award-number":["R01AA12307"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["I01 BX003014"],"award-info":[{"award-number":["I01 BX003014"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VA Merit","award":["R01AA029270"],"award-info":[{"award-number":["R01AA029270"]}]},{"name":"VA Merit","award":["R01AA12307"],"award-info":[{"award-number":["R01AA12307"]}]},{"name":"VA Merit","award":["I01 BX003014"],"award-info":[{"award-number":["I01 BX003014"]}]},{"name":"Department of Pharmacology, UTHSC","award":["R01AA029270"],"award-info":[{"award-number":["R01AA029270"]}]},{"name":"Department of Pharmacology, UTHSC","award":["R01AA12307"],"award-info":[{"award-number":["R01AA12307"]}]},{"name":"Department of Pharmacology, UTHSC","award":["I01 BX003014"],"award-info":[{"award-number":["I01 BX003014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Biological, physiological, and psychological stressors cause a \u201cstress response\u201d in our bodies. Stressors that are sensorily perceived (either acute or chronic) trigger hormonal responses from the sympathetic nervous system\u2014the SAM and HPA axis\u2014that effect intended organs to alert the individual. Other stressors have a direct effect on the target organ(s) of the body\u2014e.g., physical injury and wounds, toxins, ionizing, and UV radiation. Both kinds of stressors change cell equilibrium, often leading to reactive oxygen species (ROS) accumulation and cellular damage. Among the signaling pathways involved in fighting these stressors, the c-Jun-N-terminal kinases (JNK) respond to diverse kinds of stressors. This review focuses on JNK1 and JNK2, both of which are ubiquitously present in all cell types, and attention is paid to gastrointestinal tract epithelial cells and their response\u2014including tight junction disruption and cytoskeletal changes. We discuss the seemingly opposite roles of JNK1 and JNK2 in helping cells choose pro-survival and pro-apoptotic pathways. We examine the common features of the JNK protein structure and the possibilities of discovering JNK-isoform-specific inhibitors since, although JNK1 and JNK2 are involved in multiple diseases, including cancer, obesity, diabetes, musculoskeletal and liver disease, no cell-specific or isoform-specific inhibitors are available.<\/jats:p>","DOI":"10.3390\/biology14060649","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T03:57:34Z","timestamp":1749009454000},"page":"649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity"],"prefix":"10.3390","volume":"14","author":[{"given":"Nitesh","family":"Shashikanth","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1292-6789","authenticated-orcid":false,"given":"Osama","family":"Alaidi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lohitha","family":"Basa","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Taank","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RadhaKrishna","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Veteran Affairs Medical Center, Memphis, TN 38104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayaraman","family":"Seetharaman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Godoy, L.D., Rossignoli, M.T., Delfino-Pereira, P., Garcia-Cairasco, N., and de Lima Umeoka, E.H. (2018). A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications. Front. Behav. Neurosci., 12.","DOI":"10.3389\/fnbeh.2018.00127"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"van Herk, L., Schilder, F.P.M., de Weijer, A.D., Bruinsma, B., and Geuze, E. (2024). Heightened SAM- and HPA-axis activity during acute stress impairs decision-making: A systematic review on underlying neuropharmacological mechanisms. Neurobiol. Stress, 31.","DOI":"10.1016\/j.ynstr.2024.100659"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1080\/07420528.2018.1498098","article-title":"Modeling the influence of chronopharmacological administration of synthetic glucocorticoids on the hypothalamic-pituitary-adrenal axis","volume":"35","author":"Rao","year":"2018","journal-title":"Chronobiol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/dev.21866","article-title":"Co-activation of SAM and HPA responses to acute stress: A review of the literature and test of differential associations with preadolescents\u2019 internalizing and externalizing","volume":"61","author":"Wadsworth","year":"2019","journal-title":"Dev. Psychobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e14472","DOI":"10.1111\/psyp.14472","article-title":"The HPA and SAM axis mediate the impairment of creativity under stress","volume":"61","author":"Guo","year":"2024","journal-title":"Psychophysiology"},{"key":"ref_6","first-page":"1057","article-title":"The impact of stress on body function: A review","volume":"16","author":"Yaribeygi","year":"2017","journal-title":"EXCLI J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.celrep.2018.07.021","article-title":"Nutrient Deprivation Elicits a Transcriptional and Translational Inflammatory Response Coupled to Decreased Protein Synthesis","volume":"24","author":"Gameiro","year":"2018","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.molcel.2010.10.004","article-title":"Cellular metabolic stress: Considering how cells respond to nutrient excess","volume":"40","author":"Wellen","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31836","DOI":"10.1016\/S0021-9258(18)31771-X","article-title":"Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase\/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase","volume":"269","author":"Bird","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_10","first-page":"6683","article-title":"c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases","volume":"14","author":"Minden","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1152\/physrev.00040.2012","article-title":"Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases","volume":"94","author":"Bhattacharyya","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7210","DOI":"10.2741\/3223","article-title":"Oxidative stress-induced disruption of epithelial and endothelial tight junctions","volume":"13","author":"Rao","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12291-014-0446-0","article-title":"Free radicals: Properties, sources, targets, and their implication in various diseases","volume":"30","author":"Phaniendra","year":"2015","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.3382\/ps\/pey405","article-title":"Oxidative metabolism and efficiency: The delicate balancing act of mitochondria","volume":"98","author":"Bottje","year":"2019","journal-title":"Poult. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.gendis.2020.11.020","article-title":"Oxidative stress and mitochondrial transfer: A new dimension towards ocular diseases","volume":"9","author":"Subramaniam","year":"2022","journal-title":"Genes Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16804","DOI":"10.1074\/jbc.R117.789271","article-title":"Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions","volume":"292","author":"Wong","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Juan, C.A., Perez de la Lastra, J.M., Plou, F.J., and Perez-Lebena, E. (2021). The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094642"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aceto, G.M., Catalano, T., and Curia, M.C. (2020). Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/1726309"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Gupta, S., and Sharma, R.K. (2005). Role of oxidative stress in female reproduction. Reprod. Biol. Endocrinol., 3.","DOI":"10.1186\/1477-7827-3-28"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/15321819.2020.1726774","article-title":"Biomarkers of inflammation and oxidative stress in ophthalmic disorders","volume":"41","author":"Ahmad","year":"2020","journal-title":"J. Immunoass. Immunochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113552","DOI":"10.1016\/j.intimp.2024.113552","article-title":"A focus on c-Jun-N-terminal kinase signaling in sepsis-associated multiple organ dysfunction: Mechanisms and therapeutic strategies","volume":"143","author":"Gagnani","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cell.2004.12.041","article-title":"Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases","volume":"120","author":"Kamata","year":"2005","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2174\/0113892010331882240901095733","article-title":"Gossypetin Alleviates DSS-induced Colitis by Regulating COX2 and ROS-JNK Signaling","volume":"26","author":"Kim","year":"2024","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R105","DOI":"10.1152\/ajpregu.00395.2015","article-title":"Hyperthermia, dehydration, and osmotic stress: Unconventional sources of exercise-induced reactive oxygen species","volume":"310","author":"King","year":"2016","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00966860","article-title":"The osmotic\/calcium stress theory of brain damage: Are free radicals involved?","volume":"17","author":"Pazdernik","year":"1992","journal-title":"Neurochem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sanchez-Thomas, R., Hernandez-Garnica, M., Granados-Rivas, J.C., Saavedra, E., Penalosa-Castro, I., Rodriguez-Enriquez, S., and Moreno-Sanchez, R. (2024). Intertwining of Cellular Osmotic Stress Handling Mechanisms and Heavy Metal Accumulation. Mol. Biotechnol.","DOI":"10.1007\/s12033-024-01351-y"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1515\/BC.2006.171","article-title":"Pathogenetic interplay between osmotic and oxidative stress: The hepatic encephalopathy paradigm","volume":"387","author":"Schliess","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30232","DOI":"10.1074\/jbc.M111.240358","article-title":"CaV1.3 channels and intracellular calcium mediate osmotic stress-induced N-terminal c-Jun kinase activation and disruption of tight junctions in Caco-2 cell monolayers","volume":"286","author":"Samak","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119546","DOI":"10.1016\/j.lfs.2021.119546","article-title":"p-Coumaric acid ameliorates ionizing radiation-induced intestinal injury through modulation of oxidative stress and pyroptosis","volume":"278","author":"Li","year":"2021","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.radmp.2020.10.001","article-title":"Oxidative stress: A critical hint in ionizing radiation induced pyroptosis","volume":"1","author":"Dong","year":"2020","journal-title":"Radiat. Med. Prot."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.mam.2018.08.001","article-title":"Oxidative stress in chronic lung disease: From mitochondrial dysfunction to dysregulated redox signaling","volume":"63","author":"Anathy","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Petrovski, G., Vereb, Z., Facsko, A., and Kaarniranta, K. (2014). Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/768026"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1167\/iovs.07-1464","article-title":"Protection of human corneal epithelial cells from hypoxia-induced disruption of barrier function by keratinocyte growth factor","volume":"49","author":"Teranishi","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1158\/0008-5472.CAN-04-4453","article-title":"Identification of novel small molecule inhibitors of hypoxia-inducible factor-1 that differentially block hypoxia-inducible factor-1 activity and hypoxia-inducible factor-1alpha induction in response to hypoxic stress and growth factors","volume":"65","author":"Chau","year":"2005","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.aopr.2023.10.001","article-title":"Oxidative stress, epigenetic regulation and pathological processes of lens epithelial cells underlying diabetic cataract","volume":"3","author":"Guo","year":"2023","journal-title":"Adv. Ophthalmol. Pract. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1113\/JP271457","article-title":"The roles of c-Jun NH2-terminal kinases (JNKs) in obesity and insulin resistance","volume":"594","author":"Pal","year":"2016","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lian, P., Braber, S., Garssen, J., Wichers, H.J., Folkerts, G., Fink-Gremmels, J., and Varasteh, S. (2020). Beyond Heat Stress: Intestinal Integrity Disruption and Mechanism-Based Intervention Strategies. Nutrients, 12.","DOI":"10.3390\/nu12030734"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"113846","DOI":"10.1016\/j.ejmech.2021.113846","article-title":"The heat shock response and small molecule regulators","volume":"226","author":"Kurop","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.molcel.2010.10.006","article-title":"The heat shock response: Life on the verge of death","volume":"40","author":"Richter","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e18638","DOI":"10.7554\/eLife.18638","article-title":"Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation","volume":"5","author":"Zheng","year":"2016","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1042\/BCJ20160679","article-title":"Calcium-mediated oxidative stress: A common mechanism in tight junction disruption by different types of cellular stress","volume":"474","author":"Gangwar","year":"2017","journal-title":"Biochem. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1675230","DOI":"10.1155\/2017\/1675230","article-title":"Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells","volume":"2017","author":"Minasyan","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s11033-022-08065-x","article-title":"Progesterone regulates the endoplasmic reticulum-associated degradation and Unfolded Protein Response axis by mimicking the androgenic stimulation in prostate cancer cells","volume":"50","author":"Erzurumlu","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1177\/1947601910383011","article-title":"The Unfolded Protein Response, Degradation from Endoplasmic Reticulum and Cancer","volume":"1","author":"Tsai","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1083\/jcb.143.5.1361","article-title":"SAPK2\/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis","volume":"143","author":"Huot","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115276","DOI":"10.1016\/j.ecoenv.2023.115276","article-title":"Cinnamaldehyde alleviates zearalenone-induced LS174T cell apoptosis, barrier dysfunction and mucin reduction through JNK\/NF-kappaB signaling pathway","volume":"263","author":"Bai","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e18534","DOI":"10.1111\/jcmm.18534","article-title":"Cell-permeable JNK-inhibitory peptide regulates intestinal barrier function and inflammation to ameliorate necrotizing enterocolitis","volume":"28","author":"Bu","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"C775","DOI":"10.1152\/ajpcell.00084.2009","article-title":"Inhibition of basal p38 or JNK activity enhances epithelial barrier function through differential modulation of claudin expression","volume":"297","author":"Carrozzino","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cohen, T.S., Gray Lawrence, G., Khasgiwala, A., and Margulies, S.S. (2010). MAPK activation modulates permeability of isolated rat alveolar epithelial cell monolayers following cyclic stretch. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010385"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Elamin, E., Masclee, A., Troost, F., Pieters, H.J., Keszthelyi, D., Aleksa, K., Dekker, J., and Jonkers, D. (2014). Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: A combined in vivo and in vitro approach. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107421"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.biomaterials.2017.01.006","article-title":"Blood-brain barrier dysfunction induced by silica NPs in vitro and in vivo: Involvement of oxidative stress and Rho-kinase\/JNK signaling pathways","volume":"121","author":"Liu","year":"2017","journal-title":"Biomaterials"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"L56","DOI":"10.1152\/ajplung.00159.2010","article-title":"The Rac1\/JNK pathway is critical for EGFR-dependent barrier formation in human airway epithelial cells","volume":"300","author":"Terakado","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1016\/j.yexcr.2008.08.012","article-title":"Phosphorylation of claudin-4 is required for tight junction formation in a human keratinocyte cell line","volume":"314","author":"Aono","year":"2008","journal-title":"Exp. Cell Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1042\/BJ20140450","article-title":"Calcium\/Ask1\/MKK7\/JNK2\/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium","volume":"465","author":"Samak","year":"2015","journal-title":"Biochem. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"G947","DOI":"10.1152\/ajpgi.00396.2013","article-title":"Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism","volume":"306","author":"Samak","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"G572","DOI":"10.1152\/ajpgi.00265.2010","article-title":"c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium","volume":"299","author":"Samak","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1242\/dev.128.13.2603","article-title":"Extranuclear sequestration of phospho-Jun N-terminal kinase and distorted villi produced by activated Rac1 in the intestinal epithelium of chimeric mice","volume":"128","author":"Stappenbeck","year":"2001","journal-title":"Development"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/jcp.22273","article-title":"c-Jun N-terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells","volume":"225","author":"Kojima","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Al-Sadi, R., Ye, D., Boivin, M., Guo, S., Hashimi, M., Ereifej, L., and Ma, T.Y. (2014). Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085345"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Vyas, J., Raytthatha, N., and Prajapati, B.G. (2024). Amyloid cascade hypothesis, tau synthesis, and role of oxidative stress in AD. Alzheimers Dis. Adv. Drug Deliv. Strateg., 73\u201392.","DOI":"10.1016\/B978-0-443-13205-6.00023-6"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0896-6273(00)80727-8","article-title":"The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development","volume":"22","author":"Kuan","year":"1999","journal-title":"Neuron"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1038\/sj.onc.1205348","article-title":"Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis","volume":"21","author":"Hochedlinger","year":"2002","journal-title":"Oncogene"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.molcel.2004.08.028","article-title":"Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation","volume":"15","author":"Sabapathy","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/369156a0","article-title":"The stress-activated protein kinase subfamily of c-Jun kinases","volume":"369","author":"Kyriakis","year":"1994","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/372794a0","article-title":"Role of SAPK\/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun","volume":"372","author":"Sanchez","year":"1994","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1101\/gad.7.3.479","article-title":"JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers","volume":"7","author":"Deng","year":"1993","journal-title":"Genes Dev."},{"key":"ref_69","first-page":"G95","article-title":"Activation of activating protein 1 during hepatic acute phase response","volume":"264","author":"Hattori","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_70","first-page":"255","article-title":"Control of AP-1 activity by signal transduction cascades","volume":"28","author":"Lin","year":"1993","journal-title":"Adv. Second Messenger Phosphoprot. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e70038","DOI":"10.1002\/ddr.70038","article-title":"Bioinformatics Exploration of the Therapeutic Potential of Lotus Seed Compounds in Multiple Sclerosis: A Network Analysis of c-Jun Pathway","volume":"86","author":"Rushendran","year":"2025","journal-title":"Drug Dev. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/372798a0","article-title":"Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1","volume":"372","author":"Yan","year":"1994","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1126\/science.278.5343.1638","article-title":"Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway","volume":"278","author":"Chow","year":"1997","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1126\/science.277.5326.693","article-title":"A cytoplasmic inhibitor of the JNK signal transduction pathway","volume":"277","author":"Dickens","year":"1997","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/glia.20173","article-title":"c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia","volume":"50","author":"Waetzig","year":"2005","journal-title":"Glia"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1460-9568.2005.03857.x","article-title":"Specific pathophysiological functions of JNK isoforms in the brain","volume":"21","author":"Brecht","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1053\/j.gastro.2012.06.004","article-title":"A liver full of JNK: Signaling in regulation of cell function and disease pathogenesis, and clinical approaches","volume":"143","author":"Seki","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1128\/MMBR.00043-14","article-title":"JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships","volume":"80","author":"Zeke","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.molmet.2016.12.001","article-title":"JNK at the crossroad of obesity, insulin resistance, and cell stress response","volume":"6","author":"Solinas","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1101\/gad.7.11.2135","article-title":"Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain","volume":"7","author":"Hibi","year":"1993","journal-title":"Genes Dev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/0092-8674(94)90380-8","article-title":"JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain","volume":"76","author":"Derijard","year":"1994","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2005.7.119","article-title":"Life and death decisions: Ceramide generation and EGF receptor trafficking are modulated by oxidative stress","volume":"7","author":"Goldkorn","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/380075a0","article-title":"Requirement for ceramide-initiated SAPK\/JNK signalling in stress-induced apoptosis","volume":"380","author":"Verheij","year":"1996","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1126\/science.7914033","article-title":"A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells","volume":"265","author":"Han","year":"1994","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1101\/gad.8.24.2996","article-title":"JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation","volume":"8","author":"Kallunki","year":"1994","journal-title":"Genes Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0896-6273(95)90241-4","article-title":"p493F12 kinase: A novel MAP kinase expressed in a subset of neurons in the human nervous system","volume":"14","author":"Mohit","year":"1995","journal-title":"Neuron"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0169-328X(95)00181-Q","article-title":"Developmental expression in the mouse nervous system of the p493F12 SAP kinase","volume":"35","author":"Martin","year":"1996","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1038\/sj.emboj.7600212","article-title":"Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125","volume":"23","author":"Heo","year":"2004","journal-title":"EMBO J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.jmb.2008.08.086","article-title":"The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity","volume":"383","author":"Shaw","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0969-2126(98)00100-2","article-title":"Crystal structure of JNK3: A kinase implicated in neuronal apoptosis","volume":"6","author":"Xie","year":"1998","journal-title":"Structure"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/jb\/mvn172","article-title":"Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine gene expression in mast cells is mediated through inhibition of phosphatidylinositol 3-kinase signalling pathway","volume":"145","author":"Tanemura","year":"2009","journal-title":"J. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1021\/jm9003279","article-title":"Small molecule JNK (c-Jun N-terminal kinase) inhibitors","volume":"53","author":"Siddiqui","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1128\/MMBR.00025-06","article-title":"Uses for JNK: The many and varied substrates of the c-Jun N-terminal kinases","volume":"70","author":"Bogoyevitch","year":"2006","journal-title":"Microbiol Mol Biol Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbapap.2009.11.002","article-title":"c-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges","volume":"1804","author":"Bogoyevitch","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10987","DOI":"10.1074\/jbc.M107565200","article-title":"Identification of the critical features of a small peptide inhibitor of JNK activity","volume":"277","author":"Barr","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1042\/BST0340828","article-title":"The JIP family of MAPK scaffold proteins","volume":"34","author":"Whitmarsh","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbapap.2007.09.016","article-title":"Unique MAP Kinase binding sites","volume":"1784","author":"Akella","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e338","DOI":"10.1038\/emm.2017.20","article-title":"Roles of intestinal epithelial cells in the maintenance of gut homeostasis","volume":"49","author":"Okumura","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1152\/japplphysiol.00536.2015","article-title":"Intestinal epithelial barrier function and tight junction proteins with heat and exercise","volume":"120","author":"Dokladny","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"jcs261776","DOI":"10.1242\/jcs.261776","article-title":"A short guide to the tight junction","volume":"137","author":"Citi","year":"2024","journal-title":"J. Cell Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e977176","DOI":"10.4161\/21688370.2014.977176","article-title":"Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation","volume":"3","author":"Luettig","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"G50","DOI":"10.1152\/ajpgi.00494.2010","article-title":"ERK is involved in EGF-mediated protection of tight junctions, but not adherens junctions, in acetaldehyde-treated Caco-2 cell monolayers","volume":"301","author":"Samak","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00418-018-1736-z","article-title":"Anisomycin, a JNK and p38 activator, suppresses cell-cell junction formation in 2D cultures of K38 mouse keratinocyte cells and reduces claudin-7 expression, with an increase of paracellular permeability in 3D cultures","volume":"151","author":"Nikaido","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.4161\/cc.8.13.8928","article-title":"c-Jun N-terminal kinase mediates disassembly of apical junctions in model intestinal epithelia","volume":"8","author":"Naydenov","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Bhat, A.A., Uppada, S., Achkar, I.W., Hashem, S., Yadav, S.K., Shanmugakonar, M., Al-Naemi, H.A., Haris, M., and Uddin, S. (2018). Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01942"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Benoit, B., Baillet, A., and Pous, C. (2021). Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168375"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.ejcb.2010.10.017","article-title":"Distinct roles of JNK-1 and ERK-2 isoforms in permeability barrier repair and wound healing","volume":"90","author":"Koehler","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1158\/0008-5472.CAN-11-1982","article-title":"JNK-induced apoptosis, compensatory growth, and cancer stem cells","volume":"72","author":"Chen","year":"2012","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.molcel.2008.06.001","article-title":"JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy","volume":"30","author":"Wei","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1242\/jcs.00082","article-title":"JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms","volume":"115","author":"David","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/emboj.2009.153","article-title":"JNK signalling modulates intestinal homeostasis and tumourigenesis in mice","volume":"28","author":"Sancho","year":"2009","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"28966","DOI":"10.1074\/jbc.274.41.28966","article-title":"The JNKK2-JNK1 fusion protein acts as a constitutively active c-Jun kinase that stimulates c-Jun transcription activity","volume":"274","author":"Zheng","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2353\/ajpath.2007.061036","article-title":"c-Jun NH2-terminal kinase 1 plays a critical role in intestinal homeostasis and tumor suppression","volume":"171","author":"Tong","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5342","DOI":"10.4049\/jimmunol.168.10.5342","article-title":"p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease","volume":"168","author":"Waetzig","year":"2002","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/08941930601126140","article-title":"Genetic deletion of JNK1 and JNK2 aggravates the DSS-induced colitis in mice","volume":"20","author":"Chromik","year":"2007","journal-title":"J. Investig. Surg."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1084\/jem.20011508","article-title":"c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation","volume":"195","author":"Conze","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1053\/gast.2002.30770","article-title":"Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn\u2019s disease","volume":"122","author":"Hommes","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1096\/fj.02-0223fje","article-title":"Critical role of NF-kappaB and stress-activated protein kinases in steroid unresponsiveness","volume":"16","author":"Bantel","year":"2002","journal-title":"FASEB J."},{"key":"ref_119","first-page":"449","article-title":"Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease","volume":"17","author":"Mitsuyama","year":"2006","journal-title":"Int. J. Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1365-2567.2006.02349.x","article-title":"The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha production and epithelial cell apoptosis in acute murine colitis","volume":"118","author":"Assi","year":"2006","journal-title":"Immunology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00418-014-1219-9","article-title":"Inhibition of JNK in HaCaT cells induced tight junction formation with decreased expression of cytokeratin 5, cytokeratin 17 and desmoglein 3","volume":"142","author":"Kitagawa","year":"2014","journal-title":"Histochem. Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Hammouda, M.B., Ford, A.E., Liu, Y., and Zhang, J.Y. (2020). The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer. Cells, 9.","DOI":"10.3390\/cells9040857"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Nikoloudaki, G., Brooks, S., Peidl, A.P., Tinney, D., and Hamilton, D.W. (2020). JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031015"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"15258","DOI":"10.1074\/jbc.M512953200","article-title":"Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Smith, A.O., Jonassen, J.A., Preval, K.M., Davis, R.J., and Pazour, G.J. (2021). c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease. PLoS Genet., 17.","DOI":"10.1101\/2021.07.15.452451"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Grynberg, K., Ma, F.Y., and Nikolic-Paterson, D.J. (2017). The JNK Signaling Pathway in Renal Fibrosis. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00829"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19336918.2024.2316576","article-title":"JNK3 inhibitors as promising pharmaceuticals with neuroprotective properties","volume":"18","author":"Wu","year":"2024","journal-title":"Cell Adhes. Migr."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.molcel.2006.07.028","article-title":"JNK2 is a positive regulator of the cJun transcription factor","volume":"23","author":"Jaeschke","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_129","first-page":"455","article-title":"Context-specific inhibition of JNKs: Overcoming the dilemma of protection and damage","volume":"26","author":"Waetzig","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.brainres.2015.02.032","article-title":"Endophilin-1 regulates blood-brain barrier permeability via EGFR-JNK signaling pathway","volume":"1606","author":"Chen","year":"2015","journal-title":"Brain Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"jcs206789","DOI":"10.1242\/jcs.206789","article-title":"Phosphorylation hotspot in the C-terminal domain of occludin regulates the dynamics of epithelial junctional complexes","volume":"131","author":"Manda","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41390-024-03419-6","article-title":"Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation","volume":"97","author":"Zhang","year":"2025","journal-title":"Pediatr. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1080\/14756366.2020.1720013","article-title":"Selective inhibitors for JNK signalling: A potential targeted therapy in cancer","volume":"35","author":"Wu","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"18193","DOI":"10.1021\/acs.jmedchem.1c01716","article-title":"Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001","volume":"64","author":"Nagy","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e001060","DOI":"10.1136\/bmjresp-2021-001060","article-title":"CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: Design of a phase 2, randomised, placebo-controlled trial","volume":"9","author":"Popmihajlov","year":"2022","journal-title":"BMJ Open Respir. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"17713","DOI":"10.1021\/acs.jmedchem.4c01764","article-title":"Structure Optimization of c-Jun N-terminal Kinase 1 Inhibitors for Treating Idiopathic Pulmonary Fibrosis","volume":"67","author":"Huang","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1164\/rccm.202310-1907OC","article-title":"Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis","volume":"210","author":"Mattos","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ren, S., Liu, F., Chi, M., Liu, J., Huang, Y., Huang, W., Gu, W., Yuan, Y., Hou, S., and Chen, X. (2025). Discovery of a selective and potent inhibitor of c-Jun N-terminal kinase 1 with anti-pulmonary fibrosis effect. Bioorg. Med. Chem. Lett., 116.","DOI":"10.1016\/j.bmcl.2024.130044"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"13681","DOI":"10.1073\/pnas.251194298","article-title":"SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase","volume":"98","author":"Bennett","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1021\/acs.jmedchem.2c01834","article-title":"Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2\/3 with Selectivity over JNK1","volume":"66","author":"Lu","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1021\/acs.jctc.1c00136","article-title":"Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding","volume":"17","author":"Miller","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5710","DOI":"10.1021\/acs.jctc.2c00371","article-title":"Induced-Fit Docking Enables Accurate Free Energy Perturbation Calculations in Homology Models","volume":"18","author":"Xu","year":"2022","journal-title":"J. Chem. Theory Comput."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1016\/j.bpj.2018.02.038","article-title":"Ensemble Docking in Drug Discovery","volume":"114","author":"Amaro","year":"2018","journal-title":"Biophys. J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1021\/ci400729j","article-title":"Ensemble-based docking using biased molecular dynamics","volume":"54","author":"Campbell","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.cell.2020.04.001","article-title":"A Deep Learning Approach to Antibiotic Discovery","volume":"181","author":"Stokes","year":"2020","journal-title":"Cell"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/6\/649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:46Z","timestamp":1760032006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/6\/649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":146,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biology14060649"],"URL":"https:\/\/doi.org\/10.3390\/biology14060649","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]}}}