FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2886576780> ?p ?o ?g. }

• W2886576780 endingPage "1209" @default.
• W2886576780 startingPage "1197" @default.
• W2886576780 abstract "The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. Positive allosteric modulators (PAMs), with their potential for greater selectivity and larger therapeutic windows, may represent a viable drug development strategy, as orthosteric D1 receptor agonists possess known clinical liabilities. We discovered two structurally distinct D1 receptor PAMs, MLS6585 and MLS1082, via a high-throughput screen of the NIH Molecular Libraries program small-molecule library. Both compounds potentiate dopamine-stimulated G protein- and β-arrestin-mediated signaling and increase the affinity of dopamine for the D1 receptor with low micromolar potencies. Neither compound displayed any intrinsic agonist activity. Both compounds were also found to potentiate the efficacy of partial agonists. We tested maximally effective concentrations of each PAM in combination to determine if the compounds might act at separate or similar sites. In combination, MLS1082 + MLS6585 produced an additive potentiation of dopamine potency beyond that caused by either PAM alone for both β-arrestin recruitment and cAMP accumulation, suggesting diverse sites of action. In addition, MLS6585, but not MLS1082, had additive activity with the previously described D1 receptor PAM Compound B, suggesting that MLS1082 and Compound B may share a common binding site. A point mutation (R130Q) in the D1 receptor was found to abrogate MLS1082 activity without affecting that of MLS6585, suggesting this residue may be involved in the binding/activity of MLS1082 but not that of MLS6585. Together, MLS1082 and MLS6585 may serve as important tool compounds for the characterization of diverse allosteric sites on the D1 receptor as well as the development of optimized lead compounds for therapeutic use." @default.
• W2886576780 created "2018-08-22" @default.
• W2886576780 creator A5001184042 @default.
• W2886576780 creator A5001985394 @default.
• W2886576780 creator A5002699549 @default.
• W2886576780 creator A5011315024 @default.
• W2886576780 creator A5015562626 @default.
• W2886576780 creator A5022343281 @default.
• W2886576780 creator A5028024335 @default.
• W2886576780 creator A5034202004 @default.
• W2886576780 creator A5036261777 @default.
• W2886576780 creator A5053434971 @default.
• W2886576780 creator A5056446196 @default.
• W2886576780 creator A5076880355 @default.
• W2886576780 creator A5087938892 @default.
• W2886576780 creator A5088422127 @default.
• W2886576780 creator A5088471426 @default.
• W2886576780 creator A5089282318 @default.
• W2886576780 date "2018-08-01" @default.
• W2886576780 modified "2023-10-10" @default.
• W2886576780 title "Identification of Positive Allosteric Modulators of the D₁ Dopamine Receptor That Act at Diverse Binding Sites" @default.
• W2886576780 cites W1833104430 @default.
• W2886576780 cites W1898191473 @default.
• W2886576780 cites W1976266427 @default.
• W2886576780 cites W1977138162 @default.
• W2886576780 cites W1981952236 @default.
• W2886576780 cites W1988821183 @default.
• W2886576780 cites W2001402428 @default.
• W2886576780 cites W2002527966 @default.
• W2886576780 cites W2008123860 @default.
• W2886576780 cites W2024187762 @default.
• W2886576780 cites W2043223442 @default.
• W2886576780 cites W2046835548 @default.
• W2886576780 cites W2050650917 @default.
• W2886576780 cites W2060400255 @default.
• W2886576780 cites W2073613804 @default.
• W2886576780 cites W2087688448 @default.
• W2886576780 cites W2090132244 @default.
• W2886576780 cites W2093857837 @default.
• W2886576780 cites W2096090406 @default.
• W2886576780 cites W2097744565 @default.
• W2886576780 cites W2110319068 @default.
• W2886576780 cites W2113723602 @default.
• W2886576780 cites W2124264649 @default.
• W2886576780 cites W2135550220 @default.
• W2886576780 cites W2145094745 @default.
• W2886576780 cites W2170019144 @default.
• W2886576780 cites W2316073320 @default.
• W2886576780 cites W2492130194 @default.
• W2886576780 cites W2492634063 @default.
• W2886576780 cites W2547430990 @default.
• W2886576780 cites W2765478112 @default.
• W2886576780 cites W2774751669 @default.
• W2886576780 cites W3025891904 @default.
• W2886576780 doi "https://doi.org/10.1124/mol.118.113175" @default.
• W2886576780 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6117505" @default.
• W2886576780 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30068735" @default.
• W2886576780 hasPublicationYear "2018" @default.
• W2886576780 type Work @default.
• W2886576780 sameAs 2886576780 @default.
• W2886576780 citedByCount "32" @default.
• W2886576780 countsByYear W28865767802018 @default.
• W2886576780 countsByYear W28865767802019 @default.
• W2886576780 countsByYear W28865767802020 @default.
• W2886576780 countsByYear W28865767802021 @default.
• W2886576780 countsByYear W28865767802022 @default.
• W2886576780 countsByYear W28865767802023 @default.
• W2886576780 crossrefType "journal-article" @default.
• W2886576780 hasAuthorship W2886576780A5001184042 @default.
• W2886576780 hasAuthorship W2886576780A5001985394 @default.
• W2886576780 hasAuthorship W2886576780A5002699549 @default.
• W2886576780 hasAuthorship W2886576780A5011315024 @default.
• W2886576780 hasAuthorship W2886576780A5015562626 @default.
• W2886576780 hasAuthorship W2886576780A5022343281 @default.
• W2886576780 hasAuthorship W2886576780A5028024335 @default.
• W2886576780 hasAuthorship W2886576780A5034202004 @default.
• W2886576780 hasAuthorship W2886576780A5036261777 @default.
• W2886576780 hasAuthorship W2886576780A5053434971 @default.
• W2886576780 hasAuthorship W2886576780A5056446196 @default.
• W2886576780 hasAuthorship W2886576780A5076880355 @default.
• W2886576780 hasAuthorship W2886576780A5087938892 @default.
• W2886576780 hasAuthorship W2886576780A5088422127 @default.
• W2886576780 hasAuthorship W2886576780A5088471426 @default.
• W2886576780 hasAuthorship W2886576780A5089282318 @default.
• W2886576780 hasBestOaLocation W28865767801 @default.
• W2886576780 hasConcept C107824862 @default.
• W2886576780 hasConcept C120069818 @default.
• W2886576780 hasConcept C120750228 @default.
• W2886576780 hasConcept C160262196 @default.
• W2886576780 hasConcept C166342909 @default.
• W2886576780 hasConcept C169760540 @default.
• W2886576780 hasConcept C170493617 @default.
• W2886576780 hasConcept C185592680 @default.
• W2886576780 hasConcept C199596767 @default.
• W2886576780 hasConcept C25274449 @default.
• W2886576780 hasConcept C2776038425 @default.
• W2886576780 hasConcept C2778938600 @default.
• W2886576780 hasConcept C44208683 @default.

• next