{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:05:06Z","timestamp":1790435106240,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI181542-01"],"award-info":[{"award-number":["R21AI181542-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL62150-30A1"],"award-info":[{"award-number":["R01 HL62150-30A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs R D"],"published-print":{"date-parts":[[2024,9]]},"DOI":"10.1007\/s40268-024-00483-5","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T06:02:43Z","timestamp":1722924163000},"page":"425-434","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Preclinical and Toxicology Assessment of ALW-II-41-27, an Inhibitor of the Eph Receptor A2 (EphA2)"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-3311","authenticated-orcid":false,"given":"Theodore J.","family":"Kottom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E.","family":"Stelzig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline R.","family":"Pellegrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bindzus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhee S.","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Limper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"483_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105038","volume":"159","author":"ECW de Boer","year":"2020","unstructured":"de Boer ECW, van Gils JM, van Gils MJ. Ephrin-Eph signaling usage by a variety of viruses. Pharmacol Res. 2020;159: 105038.","journal-title":"Pharmacol Res"},{"issue":"1","key":"483_CR2","doi-asserted-by":"publisher","first-page":"5964","DOI":"10.1038\/s41467-020-19617-9","volume":"11","author":"C Su","year":"2020","unstructured":"Su C, et al. Molecular basis of EphA2 recognition by gHgL from gammaherpesviruses. Nat Commun. 2020;11(1):5964.","journal-title":"Nat Commun"},{"issue":"1","key":"483_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009221","volume":"17","author":"M Swidergall","year":"2021","unstructured":"Swidergall M, et al. Activation of EphA2-EGFR signaling in oral epithelial cells by Candida albicans virulence factors. PLoS Pathog. 2021;17(1): e1009221.","journal-title":"PLoS Pathog"},{"issue":"2","key":"483_CR4","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.celrep.2019.06.020","volume":"28","author":"M Swidergall","year":"2019","unstructured":"Swidergall M, et al. EphA2 is a neutrophil receptor for Candida albicans that stimulates antifungal activity during oropharyngeal infection. Cell Rep. 2019;28(2):423\u201333 (e5).","journal-title":"Cell Rep"},{"key":"483_CR5","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.molimm.2020.09.016","volume":"128","author":"J Zhang","year":"2020","unstructured":"Zhang J, et al. MiR-26a targets EphA2 to resist intracellular Listeria monocytogenes in macrophages. Mol Immunol. 2020;128:69\u201378.","journal-title":"Mol Immunol"},{"issue":"3","key":"483_CR6","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41564-017-0100-8","volume":"3","author":"M Swidergall","year":"2018","unstructured":"Swidergall M, et al. Publisher Correction: EphA2 is an epithelial cell pattern recognition receptor for fungal beta-glucans. Nat Microbiol. 2018;3(3):387.","journal-title":"Nat Microbiol"},{"issue":"3","key":"483_CR7","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1093\/infdis\/jiab384","volume":"225","author":"TJ Kottom","year":"2022","unstructured":"Kottom TJ, et al. EphA2 Is a lung epithelial cell receptor for pneumocystis beta-glucans. J Infect Dis. 2022;225(3):525\u201330.","journal-title":"J Infect Dis"},{"issue":"2","key":"483_CR8","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00811-23","volume":"68","author":"TJ Kottom","year":"2024","unstructured":"Kottom TJ, Carmona EM, Limper AH. Targeting host tyrosine kinase receptor EphA2 signaling via small-molecule ALW-II-41-27 inhibits macrophage pro-inflammatory signaling responses to Pneumocystis carinii beta-glucans. Antimicrob Agents Chemother. 2024;68(2): e0081123.","journal-title":"Antimicrob Agents Chemother"},{"key":"483_CR9","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01210-20","author":"TJ Kottom","year":"2020","unstructured":"Kottom TJ, Carmona EM, Limper AH. Targeting CARD9 with small-molecule therapeutics inhibits innate immune signaling and inflammatory response to Pneumocystis carinii beta-glucans. Antimicrob Agents Chemother. 2020. https:\/\/doi.org\/10.1128\/AAC.01210-20.","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"483_CR10","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1152\/jappl.1986.60.2.532","volume":"60","author":"SI Rennard","year":"1986","unstructured":"Rennard SI, et al. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol. 1986;60(2):532\u20138.","journal-title":"J Appl Physiol"},{"issue":"2","key":"483_CR11","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s40268-022-00389-0","volume":"22","author":"TJ Kottom","year":"2022","unstructured":"Kottom TJ, et al. Preclinical and toxicology studies of BRD5529, a selective inhibitor of CARD9. Drugs R D. 2022;22(2):165\u201373.","journal-title":"Drugs R D"},{"issue":"4","key":"483_CR12","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1165\/rcmb.2022-0339OC","volume":"69","author":"M Choudhury","year":"2023","unstructured":"Choudhury M, et al. Targeting pulmonary fibrosis by SLC1A5-dependent glutamine transport blockade. Am J Respir Cell Mol Biol. 2023;69(4):441\u201355.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"2","key":"483_CR13","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1096\/fj.201902354R","volume":"34","author":"JH Kang","year":"2020","unstructured":"Kang JH, et al. Transforming growth factor beta induces fibroblasts to express and release the immunomodulatory protein PD-L1 into extracellular vesicles. FASEB J. 2020;34(2):2213\u201326.","journal-title":"FASEB J"},{"issue":"3","key":"483_CR14","doi-asserted-by":"publisher","first-page":"F339","DOI":"10.1152\/ajprenal.2000.278.3.F339","volume":"278","author":"P Meneton","year":"2000","unstructured":"Meneton P, et al. Renal physiology of the mouse. Am J Physiol Renal Physiol. 2000;278(3):F339\u201351.","journal-title":"Am J Physiol Renal Physiol"},{"issue":"10","key":"483_CR15","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/PL00000229","volume":"50","author":"JA Nemzek","year":"2001","unstructured":"Nemzek JA, et al. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res. 2001;50(10):523\u20137.","journal-title":"Inflamm Res"},{"issue":"4","key":"483_CR16","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nrmicro1621","volume":"5","author":"CF Thomas Jr","year":"2007","unstructured":"Thomas CF Jr, Limper AH. Current insights into the biology and pathogenesis of Pneumocystis pneumonia. Nat Rev Microbiol. 2007;5(4):298\u2013308.","journal-title":"Nat Rev Microbiol"},{"key":"483_CR17","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00396-17","author":"HM Evans","year":"2017","unstructured":"Evans HM, et al. The trophic life cycle stage of the opportunistic fungal pathogen Pneumocystis murina hinders the ability of dendritic cells to stimulate CD4(+) t cell responses. Infect Immun. 2017. https:\/\/doi.org\/10.1128\/IAI.00396-17.","journal-title":"Infect Immun"},{"issue":"5","key":"483_CR18","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1093\/infdis\/jiw249","volume":"214","author":"G Kutty","year":"2016","unstructured":"Kutty G, et al. beta-Glucans are masked but contribute to pulmonary inflammation during Pneumocystis pneumonia. J Infect Dis. 2016;214(5):782\u201391.","journal-title":"J Infect Dis"},{"issue":"3","key":"483_CR19","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1128\/IAI.01181-12","volume":"81","author":"MJ Linke","year":"2013","unstructured":"Linke MJ, et al. Characterization of a distinct host response profile to Pneumocystis murina asci during clearance of pneumocystis pneumonia. Infect Immun. 2013;81(3):984\u201395.","journal-title":"Infect Immun"},{"issue":"21","key":"483_CR20","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJM199011223232104","volume":"323","author":"SA Bozzette","year":"1990","unstructured":"Bozzette SA, et al. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1990;323(21):1451\u20137.","journal-title":"N Engl J Med"},{"key":"483_CR21","unstructured":"Weyant RB et al. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother 2021; 1\u201314."},{"issue":"1","key":"483_CR22","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1164\/rccm.2008-740ST","volume":"183","author":"AH Limper","year":"2011","unstructured":"Limper AH, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183(1):96\u2013128.","journal-title":"Am J Respir Crit Care Med"},{"issue":"7","key":"483_CR23","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.4049\/jimmunol.2001373","volume":"206","author":"W Sun","year":"2021","unstructured":"Sun W, et al. Cutting edge: EPHB2 is a coreceptor for fungal recognition and phosphorylation of SYK in the dectin-1 signaling pathway. J Immunol. 2021;206(7):1419\u201323.","journal-title":"J Immunol"},{"issue":"12","key":"483_CR24","doi-asserted-by":"publisher","first-page":"13644","DOI":"10.1096\/fj.201901192R","volume":"33","author":"L Zhang","year":"2019","unstructured":"Zhang L, et al. EphrinB2\/ephB2-mediated myenteric synaptic plasticity: mechanisms underlying the persistent muscle hypercontractility and pain in postinfectious IBS. FASEB J. 2019;33(12):13644\u201359.","journal-title":"FASEB J"}],"container-title":["Drugs in R&D"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40268-024-00483-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40268-024-00483-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40268-024-00483-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T20:06:46Z","timestamp":1728158806000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40268-024-00483-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["483"],"URL":"https:\/\/doi.org\/10.1007\/s40268-024-00483-5","relation":{},"ISSN":["1174-5886","1179-6901"],"issn-type":[{"value":"1174-5886","type":"print"},{"value":"1179-6901","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"assertion":[{"value":"28 July 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This work was supported by the Mayo Foundation; the Walter and Leonore Annenberg Foundation, and NIH grants R21AI181542-01 and R01 HL62150-30A1 to A.H.L.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the Mayo Clinic Institutional Animal Care and Use Committee (IACUC) approved protocol A00007116-23 on 9\/5\/2023.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The datasets generated and\/or analyzed during the current study are available from the corresponding author on reasonable request.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"T.J.K., K.E.S., M.R.P., M.B., E.S.Y., and A.H.L. made substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data. All authors approved the version to be published.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}