FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3147652885> ?p ?o ?g. }

• W3147652885 endingPage "116132" @default.
• W3147652885 startingPage "116132" @default.
• W3147652885 abstract "Since 2007, Metalloproteases (MMPs) have been considered potential targets for treating osteoarthritis (OA), for which the primary pathogenic event is the extensive degeneration of articular cartilage. MMP3 is an enzyme critical for these degenerative changes. However, problems of selectivity, low bioavailability and poor metabolic profile during clinical trials of MMPs inhibitors (MMPIs) led to limited beneficial effect and thus did not justify further pursuit of the clinical studies. In a previous work, a new alkyl derivative of hyaluronic acid (HA), HYADD4®, previously approved as intra-articular treatment for knee OA, was studied in vitro and in vivo as MMP3I. Molecular simulation studies confirmed the interaction between the alkyl side chain of this HA derivative and the additional S1′ pocket of MMP3. However, the high MW and the polar HA backbone of HYADD4® imply a high desolvation energy cost, which can potentially decrease its inhibitory potency. In this study, a new class of MMP3Is based on a small peptide backbone (CGV) chemically derivatized with an alkyl chain was developed through interactive cycles of design, synthesis and screening, accompanied by computational evaluation and optimization. Two MMP3Is, e(I) and l(II), were selected because of their effective inhibitory activity (3.2 and 10.2 µM, respectively) and water solubility. Both MMPIs showed a broad range of inhibitory effects against almost all the MMPs tested. In an in vitro model of inflammatory OA, e(I) was the most effective MMPI: at the concentration of 93 µM, it reversed inflammatory outcomes. Moreover, because of its amphiphilic structure, the e(I) MMPI promoted stable micellar formulation at concentrations higher than 0.2 mg/mL in water. The findings were confirmed by TEM and Nile red staining analysis. Based on these results, the e(I) MMPI can be considered a good candidate for the intra-articular treatment of OA, and the micellar formulation of this peptide in an aqueous buffer can potentially increase the bioavailability and, thus, the efficacy of the MMPIs." @default.
• W3147652885 created "2021-04-13" @default.
• W3147652885 creator A5008583952 @default.
• W3147652885 creator A5019871088 @default.
• W3147652885 creator A5021413221 @default.
• W3147652885 creator A5031814668 @default.
• W3147652885 creator A5038067150 @default.
• W3147652885 creator A5056145245 @default.
• W3147652885 creator A5078709195 @default.
• W3147652885 creator A5082402311 @default.
• W3147652885 creator A5084058370 @default.
• W3147652885 date "2021-05-01" @default.
• W3147652885 modified "2023-10-01" @default.
• W3147652885 title "Amphiphilic peptide-based MMP3 inhibitors for intra-articular treatment of knee OA" @default.
• W3147652885 cites W1976102173 @default.
• W3147652885 cites W2002670516 @default.
• W3147652885 cites W2011569383 @default.
• W3147652885 cites W2015375238 @default.
• W3147652885 cites W2016063920 @default.
• W3147652885 cites W2021657783 @default.
• W3147652885 cites W2028149799 @default.
• W3147652885 cites W2050456292 @default.
• W3147652885 cites W2060200790 @default.
• W3147652885 cites W2069004304 @default.
• W3147652885 cites W2071359561 @default.
• W3147652885 cites W2095512005 @default.
• W3147652885 cites W2121040393 @default.
• W3147652885 cites W2125341725 @default.
• W3147652885 cites W2140898147 @default.
• W3147652885 cites W2148191159 @default.
• W3147652885 cites W2154401382 @default.
• W3147652885 cites W2155351009 @default.
• W3147652885 cites W2160907977 @default.
• W3147652885 cites W2170108866 @default.
• W3147652885 cites W2323491683 @default.
• W3147652885 cites W2801771106 @default.
• W3147652885 cites W2894714028 @default.
• W3147652885 cites W2953342712 @default.
• W3147652885 cites W2970104014 @default.
• W3147652885 doi "https://doi.org/10.1016/j.bmc.2021.116132" @default.
• W3147652885 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33872958" @default.
• W3147652885 hasPublicationYear "2021" @default.
• W3147652885 type Work @default.
• W3147652885 sameAs 3147652885 @default.
• W3147652885 citedByCount "3" @default.
• W3147652885 countsByYear W31476528852022 @default.
• W3147652885 countsByYear W31476528852023 @default.
• W3147652885 crossrefType "journal-article" @default.
• W3147652885 hasAuthorship W3147652885A5008583952 @default.
• W3147652885 hasAuthorship W3147652885A5019871088 @default.
• W3147652885 hasAuthorship W3147652885A5021413221 @default.
• W3147652885 hasAuthorship W3147652885A5031814668 @default.
• W3147652885 hasAuthorship W3147652885A5038067150 @default.
• W3147652885 hasAuthorship W3147652885A5056145245 @default.
• W3147652885 hasAuthorship W3147652885A5078709195 @default.
• W3147652885 hasAuthorship W3147652885A5082402311 @default.
• W3147652885 hasAuthorship W3147652885A5084058370 @default.
• W3147652885 hasConcept C104317684 @default.
• W3147652885 hasConcept C105702510 @default.
• W3147652885 hasConcept C109523444 @default.
• W3147652885 hasConcept C142724271 @default.
• W3147652885 hasConcept C150194340 @default.
• W3147652885 hasConcept C150903083 @default.
• W3147652885 hasConcept C15920480 @default.
• W3147652885 hasConcept C178790620 @default.
• W3147652885 hasConcept C181389837 @default.
• W3147652885 hasConcept C185592680 @default.
• W3147652885 hasConcept C202751555 @default.
• W3147652885 hasConcept C204787440 @default.
• W3147652885 hasConcept C207001950 @default.
• W3147652885 hasConcept C2776164576 @default.
• W3147652885 hasConcept C2777529286 @default.
• W3147652885 hasConcept C2779281246 @default.
• W3147652885 hasConcept C2779295440 @default.
• W3147652885 hasConcept C521977710 @default.
• W3147652885 hasConcept C55493867 @default.
• W3147652885 hasConcept C67407626 @default.
• W3147652885 hasConcept C71924100 @default.
• W3147652885 hasConcept C86803240 @default.
• W3147652885 hasConcept C98274493 @default.
• W3147652885 hasConceptScore W3147652885C104317684 @default.
• W3147652885 hasConceptScore W3147652885C105702510 @default.
• W3147652885 hasConceptScore W3147652885C109523444 @default.
• W3147652885 hasConceptScore W3147652885C142724271 @default.
• W3147652885 hasConceptScore W3147652885C150194340 @default.
• W3147652885 hasConceptScore W3147652885C150903083 @default.
• W3147652885 hasConceptScore W3147652885C15920480 @default.
• W3147652885 hasConceptScore W3147652885C178790620 @default.
• W3147652885 hasConceptScore W3147652885C181389837 @default.
• W3147652885 hasConceptScore W3147652885C185592680 @default.
• W3147652885 hasConceptScore W3147652885C202751555 @default.
• W3147652885 hasConceptScore W3147652885C204787440 @default.
• W3147652885 hasConceptScore W3147652885C207001950 @default.
• W3147652885 hasConceptScore W3147652885C2776164576 @default.
• W3147652885 hasConceptScore W3147652885C2777529286 @default.
• W3147652885 hasConceptScore W3147652885C2779281246 @default.
• W3147652885 hasConceptScore W3147652885C2779295440 @default.
• W3147652885 hasConceptScore W3147652885C521977710 @default.

• next