{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:21:33Z","timestamp":1792689693013,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,18]],"date-time":"2018-02-18T00:00:00Z","timestamp":1518912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones.<\/jats:p>","DOI":"10.3390\/molecules23020453","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T03:54:22Z","timestamp":1519098862000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening"],"prefix":"10.3390","volume":"23","author":[{"given":"Josiane","family":"Cruz","sequence":"first","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moys\u00e9s","family":"Neto","sequence":"additional","affiliation":[{"name":"Laboratory Molecular Modeling, Estadual University of Feira de Santana, Bahia 44036-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciane","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-1320","authenticated-orcid":false,"given":"Ryan","family":"Da S. 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Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi","family":"Brasil","sequence":"additional","affiliation":[{"name":"Institute of Technology, Federal University of Par\u00e1, Par\u00e1, Amazon, Bel\u00e9m 66075-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleison","family":"Lobato","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4182-376X","authenticated-orcid":false,"given":"Glauber","family":"Da Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Bittencourt","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo 14040-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Leite","sequence":"additional","affiliation":[{"name":"Laboratory Molecular Modeling, Estadual University of Feira de Santana, Bahia 44036-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-335X","authenticated-orcid":false,"given":"Cleydson","family":"Santos","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Federal University of Amap\u00e1, Macap\u00e1, Amap\u00e1 68902-280, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29651","DOI":"10.1074\/jbc.M114.591388","article-title":"In vivo inhibition of RIPK2 kinase alleviates inflammatory disease","volume":"289","author":"Benderitter","year":"2014","journal-title":"J. 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