دورية أكاديمية
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Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening.

التفاصيل البيبلوغرافية
العنوان: Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening.
المؤلفون: Cruz JV; Postgraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. josianeviana2007@gmail.com.; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. josianeviana2007@gmail.com., Neto MFA; Laboratory Molecular Modeling, Estadual University of Feira de Santana, Bahia 44036-900, Brazil. moysesfagundes@gmail.com., Silva LB; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. luciaanebarros@hotmail.com., da S Ramos R; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. ryanquimico@hotmail.com., da S Costa J; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. josivan.chemistry@gmail.com., Brasil DSB; Institute of Technology, Federal University of Pará, Pará, Amazon, Belém 66075-900, Brazil. dsbbrasil@ig.com.br., Lobato CC; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. cleyson.cl@gmail.com., da Costa GV; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. vilhenac@hotmail.com., Bittencourt JAHM; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. joseadolfo@unifap.br., da Silva CHTP; Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-020, Brazil. tomich@fcfrp.usp.br., Leite FHA; Laboratory Molecular Modeling, Estadual University of Feira de Santana, Bahia 44036-900, Brazil. fhpharm@gmail.com., Santos CBR; Postgraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. breno@unifap.br.; Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá, Amapá 68902-280, Brazil. breno@unifap.br.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2018 Feb 18; Vol. 23 (2). Date of Electronic Publication: 2018 Feb 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Imidazoles/*chemistry , Inflammation/*drug therapy , Protein Kinase Inhibitors/*chemistry , Pyridazines/*chemistry , Receptor-Interacting Protein Serine-Threonine Kinase 2/*antagonists & inhibitors, Crystallography, X-Ray ; Humans ; Imidazoles/therapeutic use ; Molecular Docking Simulation ; Protein Kinase Inhibitors/therapeutic use ; Pyridazines/therapeutic use ; Receptor-Interacting Protein Serine-Threonine Kinase 2/chemistry ; Signal Transduction/drug effects ; User-Computer Interface
مستخلص: 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.
Competing Interests: The authors declare no conflict of interest.
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فهرسة مساهمة: Keywords: RIPK2; WEHI-345; anti-inflammatory; ponatinib; rheumatoid arthritis; virtual screening
المشرفين على المادة: 0 (Imidazoles)
0 (Protein Kinase Inhibitors)
0 (Pyridazines)
4340891KFS (ponatinib)
EC 2.7.11.1 (RIPK2 protein, human)
EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2)
تواريخ الأحداث: Date Created: 20180222 Date Completed: 20180813 Latest Revision: 20181207
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6017386
DOI: 10.3390/molecules23020453
PMID: 29463017
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules23020453