FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2099886404> ?p ?o ?g. }

• W2099886404 endingPage "1453" @default.
• W2099886404 startingPage "1441" @default.
• W2099886404 abstract "Chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) has attracted interest as a potential therapeutic target in inflammatory diseases. Ramatroban, a thromboxane A₂ receptor antagonist with clinical efficacy in allergic rhinitis, was recently found to also display potent CRTH2 antagonistic activity. Here, we present the pharmacological profile of three ramatroban analogs that differ chemically from ramatroban by either a single additional methyl group (TM30642), or an acetic acid instead of a propionic acid side chain (TM30643), or both modifications (TM30089). All three compounds bound to human CRTH2 stably expressed in human embryonic kidney 293 cells with nanomolar affinity. [³H]Prostaglandin D₂ (PGD2) saturation analysis reveals that ramatroban and TM30642 decrease PGD2 affinity, whereas TM30643 and TM30089 exclusively depress ligand binding capacity (<i>B</i>_max). Each of the three compounds acted as potent CRTH2 antagonists, yet the nature of their antagonism differed markedly. In functional assays measuring inhibition of PGD2-mediated 1) guanosine 5′-<i>O</i>-(3-thio)triphosphate binding, 2) β-arrestin translocation, and 3) shape change of human eosinophils endogenously expressing CRTH2, ramatroban, and TM30642 produced surmountable antagonism and parallel rightward shifts of the PGD2 concentration-response curves. For TM30643 and TM30089, this shift was accompanied by a progressive reduction of maximal response. Binding analyses indicated that the functional insurmountability of TM30643 and TM30089 was probably related to long-lasting CRTH2 inhibition mediated via the orthosteric site of the receptor. A mechanistic understanding of insurmountability of CRTH2 antagonists could be fundamental for development of this novel class of anti-inflammatory drugs." @default.
• W2099886404 created "2016-06-24" @default.
• W2099886404 creator A5006321692 @default.
• W2099886404 creator A5016649280 @default.
• W2099886404 creator A5016689951 @default.
• W2099886404 creator A5030748994 @default.
• W2099886404 creator A5041231391 @default.
• W2099886404 creator A5046444163 @default.
• W2099886404 creator A5053521024 @default.
• W2099886404 creator A5054216760 @default.
• W2099886404 date "2006-01-17" @default.
• W2099886404 modified "2023-10-03" @default.
• W2099886404 title "On the Mechanism of Interaction of Potent Surmountable and Insurmountable Antagonists with the Prostaglandin D2 Receptor CRTH2" @default.
• W2099886404 cites W1835964184 @default.
• W2099886404 cites W1970924302 @default.
• W2099886404 cites W1971595233 @default.
• W2099886404 cites W1994527338 @default.
• W2099886404 cites W2012768613 @default.
• W2099886404 cites W2014810793 @default.
• W2099886404 cites W2018464738 @default.
• W2099886404 cites W2022772025 @default.
• W2099886404 cites W2030571587 @default.
• W2099886404 cites W2031418023 @default.
• W2099886404 cites W2041904720 @default.
• W2099886404 cites W2042154246 @default.
• W2099886404 cites W2042738623 @default.
• W2099886404 cites W2048358065 @default.
• W2099886404 cites W2049161169 @default.
• W2099886404 cites W2056423354 @default.
• W2099886404 cites W2063924884 @default.
• W2099886404 cites W2103069823 @default.
• W2099886404 cites W2111777001 @default.
• W2099886404 cites W2113345150 @default.
• W2099886404 cites W2126564233 @default.
• W2099886404 cites W2128663076 @default.
• W2099886404 cites W2129508497 @default.
• W2099886404 cites W2150068375 @default.
• W2099886404 cites W2154435458 @default.
• W2099886404 cites W2156797817 @default.
• W2099886404 cites W2163335530 @default.
• W2099886404 cites W2164102008 @default.
• W2099886404 cites W2166893697 @default.
• W2099886404 cites W2170105701 @default.
• W2099886404 cites W2341665280 @default.
• W2099886404 doi "https://doi.org/10.1124/mol.105.017681" @default.
• W2099886404 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16418339" @default.
• W2099886404 hasPublicationYear "2006" @default.
• W2099886404 type Work @default.
• W2099886404 sameAs 2099886404 @default.
• W2099886404 citedByCount "48" @default.
• W2099886404 countsByYear W20998864042013 @default.
• W2099886404 countsByYear W20998864042014 @default.
• W2099886404 countsByYear W20998864042015 @default.
• W2099886404 countsByYear W20998864042016 @default.
• W2099886404 countsByYear W20998864042017 @default.
• W2099886404 countsByYear W20998864042018 @default.
• W2099886404 countsByYear W20998864042019 @default.
• W2099886404 countsByYear W20998864042020 @default.
• W2099886404 countsByYear W20998864042021 @default.
• W2099886404 countsByYear W20998864042022 @default.
• W2099886404 countsByYear W20998864042023 @default.
• W2099886404 crossrefType "journal-article" @default.
• W2099886404 hasAuthorship W2099886404A5006321692 @default.
• W2099886404 hasAuthorship W2099886404A5016649280 @default.
• W2099886404 hasAuthorship W2099886404A5016689951 @default.
• W2099886404 hasAuthorship W2099886404A5030748994 @default.
• W2099886404 hasAuthorship W2099886404A5041231391 @default.
• W2099886404 hasAuthorship W2099886404A5046444163 @default.
• W2099886404 hasAuthorship W2099886404A5053521024 @default.
• W2099886404 hasAuthorship W2099886404A5054216760 @default.
• W2099886404 hasConcept C170493617 @default.
• W2099886404 hasConcept C185592680 @default.
• W2099886404 hasConcept C2107291 @default.
• W2099886404 hasConcept C2776885963 @default.
• W2099886404 hasConcept C2777361909 @default.
• W2099886404 hasConcept C2777383412 @default.
• W2099886404 hasConcept C2777995097 @default.
• W2099886404 hasConcept C2780664492 @default.
• W2099886404 hasConcept C55493867 @default.
• W2099886404 hasConcept C71240020 @default.
• W2099886404 hasConcept C86803240 @default.
• W2099886404 hasConcept C95444343 @default.
• W2099886404 hasConcept C98274493 @default.
• W2099886404 hasConceptScore W2099886404C170493617 @default.
• W2099886404 hasConceptScore W2099886404C185592680 @default.
• W2099886404 hasConceptScore W2099886404C2107291 @default.
• W2099886404 hasConceptScore W2099886404C2776885963 @default.
• W2099886404 hasConceptScore W2099886404C2777361909 @default.
• W2099886404 hasConceptScore W2099886404C2777383412 @default.
• W2099886404 hasConceptScore W2099886404C2777995097 @default.
• W2099886404 hasConceptScore W2099886404C2780664492 @default.
• W2099886404 hasConceptScore W2099886404C55493867 @default.
• W2099886404 hasConceptScore W2099886404C71240020 @default.
• W2099886404 hasConceptScore W2099886404C86803240 @default.
• W2099886404 hasConceptScore W2099886404C95444343 @default.
• W2099886404 hasConceptScore W2099886404C98274493 @default.
• W2099886404 hasIssue "4" @default.
• W2099886404 hasLocation W20998864041 @default.

• next