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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Josiane V CruzCleydson B R Santos

Abstract

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 crystallog...Continue Reading

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Citations

Jan 30, 2019·Pharmaceuticals·Ryan da Silva RamosWilliams Jorge da Cruz Macêdo
Mar 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kelton L B Dos SantosCleydson B R Santos
Jun 30, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Samuel K KwofieMichael D Wilson
Nov 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Josivan da Silva CostaCleydson Breno Rodrigues Dos Santos
Jan 6, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rosivaldo S BorgesCleydson B R Santos
Feb 8, 2020·Journal of Biomolecular Structure & Dynamics·Hady KeitaJosé Carlos Tavares Carvalho
Sep 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pedro H F AraújoCleydson B R Santos
Aug 30, 2020·Pharmaceuticals·Rozires P LeãoCleydson B R Santos
Apr 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·José A H M BittencourtCleydson B R Santos
Aug 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elenilze F B FerreiraCleydson B R Santos
Jan 12, 2021·Journal of Biomolecular Structure & Dynamics·Josiane V CruzCleydson B R Santos
May 15, 2021·Journal of Biomolecular Structure & Dynamics·Prosper Obed ChukwuemekaFunmilayo Janet Adeojo

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Software Mentioned

QikProp
NP
Discovery Studio
Prediction of Activity Spectral for Substances ( PASS )
DEREK
® Sketch
SYBYL
DUD
Marvin
SigmaPlot

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