{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:18:49Z","timestamp":1790691529891,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:00:00Z","timestamp":1493683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA154387"],"award-info":[{"award-number":["R01CA154387"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0176694","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T13:27:55Z","timestamp":1493731675000},"page":"e0176694","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Small molecule inhibitors of mesotrypsin from a structure-based docking screen"],"prefix":"10.1371","volume":"12","author":[{"given":"Olumide","family":"Kayode","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunnan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei S.","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Caulfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Bode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-109X","authenticated-orcid":true,"given":"Evette S.","family":"Radisky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,5,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0016-5085(84)80117-1","article-title":"Mesotrypsin: A new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid","volume":"86","author":"H Rinderknecht","year":"1984","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1006\/jmbi.2001.5305","article-title":"Crystal structure reveals basis for the inhibitor resistance of human brain trypsin","volume":"315","author":"G Katona","year":"2002","journal-title":"J Mol Biol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"48580","DOI":"10.1074\/jbc.M310301200","article-title":"Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors","volume":"278","author":"R Szmola","year":"2003","journal-title":"J Biol Chem"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/sj.bjp.0706410","article-title":"Activity of recombinant trypsin isoforms on human proteinase-activated receptors (par): Mesotrypsin cannot activate epithelial par-1, -2, but weakly activates brain par-1","volume":"146","author":"Z Grishina","year":"2005","journal-title":"Br J Pharmacol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"26089","DOI":"10.1074\/jbc.M703840200","article-title":"Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia","volume":"282","author":"W Knecht","year":"2007","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1074\/jbc.M708268200","article-title":"Structural basis for accelerated cleavage of bovine pancreatic trypsin inhibitor (bpti) by human mesotrypsin","volume":"283","author":"MA Salameh","year":"2008","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1074\/jbc.M109.057216","article-title":"The amyloid precursor protein\/protease nexin 2 kunitz inhibitor domain is a highly specific substrate of mesotrypsin","volume":"285","author":"MA Salameh","year":"2010","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"32783","DOI":"10.1074\/jbc.M114.609560","article-title":"Sequence and conformational specificity in substrate recognition: Several human kunitz protease inhibitor domains are specific substrates of mesotrypsin","volume":"289","author":"D Pendlebury","year":"2014","journal-title":"J Biol Chem"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"28389","DOI":"10.18632\/oncotarget.4949","article-title":"Trypsinogen 4 boosts tumor endothelial cells migration through proteolysis of tissue factor pathway inhibitor-2","volume":"6","author":"C Ghilardi","year":"2015","journal-title":"Oncotarget"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1038\/jid.2014.3","article-title":"Keratinocyte-specific mesotrypsin contributes to the desquamation process via kallikrein activation and lekti degradation","volume":"134","author":"M Miyai","year":"2014","journal-title":"J Invest Dermatol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1111\/j.1742-4658.2007.05708.x","article-title":"Unconventional translation initiation of human trypsinogen 4 at a cug codon with an n-terminal leucine. A possible means to regulate gene expression","volume":"274","author":"AL Nemeth","year":"2007","journal-title":"Febs J"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/jid.2009.364","article-title":"Keratinocytes synthesize enteropeptidase and multiple forms of trypsinogen during terminal differentiation","volume":"130","author":"J Nakanishi","year":"2010","journal-title":"J Invest Dermatol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e1181","DOI":"10.1038\/cddis.2014.145","article-title":"Multiple pathways are involved in DNA degradation during keratinocyte terminal differentiation","volume":"5","author":"M Yamamoto-Tanaka","year":"2014","journal-title":"Cell Death Dis"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"20026","DOI":"10.1074\/jbc.M113.543421","article-title":"Mesotrypsin and caspase-14 participate in prosaposin processing: Potential relevance to epidermal permeability barrier formation","volume":"289","author":"M Yamamoto-Tanaka","year":"2014","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5564","DOI":"10.1158\/0008-5472.CAN-04-2004","article-title":"S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer","volume":"64","author":"S Diederichs","year":"2004","journal-title":"Cancer Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10549-009-0699-0","article-title":"Mesotrypsin promotes malignant growth of breast cancer cells through shedding of cd109","volume":"124","author":"A Hockla","year":"2010","journal-title":"Breast Cancer Res Treat"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e76667","DOI":"10.1371\/journal.pone.0076667","article-title":"Autocrine extra-pancreatic trypsin 3 secretion promotes cell proliferation and survival in esophageal adenocarcinoma","volume":"8","author":"S Han","year":"2013","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1136\/gut.2009.200105","article-title":"Prss3 promotes tumour growth and metastasis of human pancreatic cancer","volume":"59","author":"G Jiang","year":"2010","journal-title":"Gut"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1158\/1541-7786.MCR-12-0314","article-title":"PRSS3\/mesotrypsin is a therapeutic target for metastatic prostate cancer","volume":"10","author":"A Hockla","year":"2012","journal-title":"Mol Cancer Res"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.ygyno.2015.02.022","article-title":"Prss3 expression is associated with tumor progression and poor prognosis in epithelial ovarian cancer","volume":"137","author":"R Ma","year":"2015","journal-title":"Gynecol Oncol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"36884","DOI":"10.1074\/jbc.M110.171348","article-title":"Determinants of affinity and proteolytic stability in interactions of kunitz family protease inhibitors with mesotrypsin","volume":"285","author":"MA Salameh","year":"2010","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/BJ20110788","article-title":"The p2' residue is a key determinant of mesotrypsin specificity: Engineering a high-affinity inhibitor with anticancer activity","volume":"440","author":"MA Salameh","year":"2011","journal-title":"Biochem J"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1042\/BJ20151410","article-title":"Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy","volume":"473","author":"I Cohen","year":"2016","journal-title":"Biochem J"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1515\/bc.2010.030","article-title":"Identification of novel peptide inhibitors for human trypsins","volume":"391","author":"P Wu","year":"2010","journal-title":"Biol Chem"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/cbdd.12055","article-title":"The future of peptide-based drugs","volume":"81","author":"DJ Craik","year":"2013","journal-title":"Chem Biol Drug Des"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4839","DOI":"10.1016\/j.bmcl.2012.05.046","article-title":"Discovery of benzothiazole guanidines as novel inhibitors of thrombin and trypsin iv","volume":"22","author":"M Karle","year":"2012","journal-title":"Bioorg Med Chem Lett"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1002\/pro.5560070411","article-title":"Flexible ligand docking using conformational ensembles","volume":"7","author":"DM Lorber","year":"1998","journal-title":"Protein Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"RA Friesner","year":"2004","journal-title":"J Med Chem"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"RA Friesner","year":"2006","journal-title":"J Med Chem"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0014-5793(98)00914-4","article-title":"A trypanosome oligopeptidase as a target for the trypanocidal agents pentamidine, diminazene and suramin","volume":"433","author":"RE Morty","year":"1998","journal-title":"FEBS Lett"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.ijbiomac.2010.03.006","article-title":"Structural binding evidence of the trypanocidal drugs berenil and pentacarinate active principles to a serine protease model","volume":"46","author":"CS Perilo","year":"2010","journal-title":"Int J Biol Macromol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1021\/cr0104375","article-title":"Cis-trans isomerization of organic molecules and biomolecules: Implications and applications","volume":"103","author":"C Dugave","year":"2003","journal-title":"Chem Rev"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"5739","DOI":"10.1021\/jo000599l","article-title":"Kinetic studies on the thermal cis-trans isomerization of 1, 3-diphenyltriazene in aqueous solution. Effects of acids and bases","volume":"65","author":"M Barra","year":"2000","journal-title":"The Journal of organic chemistry"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"21523","DOI":"10.1074\/jbc.M115.662429","article-title":"Mesotrypsin has evolved four unique residues to cleave trypsin inhibitors as substrates","volume":"290","author":"AP Alloy","year":"2015","journal-title":"J Biol Chem"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1016\/j.bmcl.2011.04.088","article-title":"Discovery of xen907, a spirooxindole blocker of nav1.7 for the treatment of pain","volume":"21","author":"S Chowdhury","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1021\/jm4011862","article-title":"Conformation-based restrictions and scaffold replacements in the design of hepatitis c virus polymerase inhibitors: Discovery of deleobuvir (bi 207127)","volume":"57","author":"SR LaPlante","year":"2014","journal-title":"J Med Chem"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1021\/jm401338c","article-title":"Ligand bioactive conformation plays a critical role in the design of drugs that target the hepatitis c virus ns3 protease","volume":"57","author":"SR LaPlante","year":"2014","journal-title":"J Med Chem"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"5094","DOI":"10.1021\/jm401733v","article-title":"Synthesis of rigidified eif4e\/eif4g inhibitor-1 (4egi-1) mimetic and their in vitro characterization as inhibitors of protein-protein interaction","volume":"57","author":"P Mahalingam","year":"2014","journal-title":"J Med Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"26304","DOI":"10.1074\/jbc.M116.758417","article-title":"An acrobatic substrate metamorphosis reveals a requirement for substrate conformational dynamics in trypsin proteolysis","volume":"291","author":"O Kayode","year":"2016","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"HM Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref41","first-page":"307","article-title":"Processing of x-ray diffraction data collected in oscillation mode","volume":"276","author":"Z Otwinowski","year":"1997","journal-title":"Methods in Enzymology, Volume 276: Macromolecular Crystallography, part A, p 307\u2013326, 1997"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1107\/S0907444909042589","article-title":"Molecular replacement with molrep","volume":"66","author":"A Vagin","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"P Emsley","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of coot","volume":"66","author":"P Emsley","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement of macromolecular structures by the maximum-likelihood method","volume":"53","author":"GN Murshudov","year":"1997","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.str.2011.08.006","article-title":"A new generation of crystallographic validation tools for the protein data bank","volume":"19","author":"RJ Read","year":"2011","journal-title":"Structure"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0176694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:06:21Z","timestamp":1658966781000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0176694"}},"subtitle":[],"editor":[{"given":"Matthew","family":"Bogyo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,5,2]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0176694","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,2]]}}}