MLS 1547 - CAS 315698-36-3
Category: Inhibitor
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Molecular Formula:
C19H19ClN4O
Molecular Weight:
354.83
COA:
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Targets:
Dopamine Receptor
Description:
MLS 1547 is a dopamine D2 receptor agonist. It may be used in the combination with antipsychotic drugs.
Purity:
≥98% by HPLC
Synonyms:
MLS 1547; MLS1547; MLS-1547; 5-Chloro-7-[[4-(2-pyridinyl)-1-piperazinyl]methyl]-8-quinolinol
MSDS:
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InChIKey:
OPEJNANYABTIGC-UHFFFAOYSA-N
InChI:
InChI=1S/C19H19ClN4O/c20-16-12-14(19(25)18-15(16)4-3-7-22-18)13-23-8-10-24(11-9-23)17-5-1-2-6-21-17/h1-7,12,25H,8-11,13H2
Canonical SMILES:
C1CN(CCN1CC2=CC(=C3C=CC=NC3=C2O)Cl)C4=CC=CC=N4
1.Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor.
Free RB;Chun LS;Moritz AE;Miller BN;Doyle TB;Conroy JL;Padron A;Meade JA;Xiao J;Hu X;Dulcey AE;Han Y;Duan L;Titus S;Bryant-Genevier M;Barnaeva E;Ferrer M;Javitch JA;Beuming T;Shi L;Southall NT;Marugan JJ;Sibley DR Mol Pharmacol. 2014 Jul;86(1):96-105. doi: 10.1124/mol.113.090563. Epub 2014 Apr 22.
A high-throughput screening campaign was conducted to interrogate a 380,000+ small-molecule library for novel D2 dopamine receptor modulators using a calcium mobilization assay. Active agonist compounds from the primary screen were examined for orthogonal D2 dopamine receptor signaling activities including cAMP modulation and β-arrestin recruitment. Although the majority of the subsequently confirmed hits activated all signaling pathways tested, several compounds showed a diminished ability to stimulate β-arrestin recruitment. One such compound (MLS1547; 5-chloro-7-[(4-pyridin-2-ylpiperazin-1-yl)methyl]quinolin-8-ol) is a highly efficacious agonist at D2 receptor-mediated G protein-linked signaling, but does not recruit β-arrestin as demonstrated using two different assays. This compound does, however, antagonize dopamine-stimulated β-arrestin recruitment to the D2 receptor. In an effort to investigate the chemical scaffold of MLS1547 further, we characterized a set of 24 analogs of MLS1547 with respect to their ability to inhibit cAMP accumulation or stimulate β-arrestin recruitment. A number of the analogs were similar to MLS1547 in that they displayed agonist activity for inhibiting cAMP accumulation, but did not stimulate β-arrestin recruitment (i.
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CAS 315698-36-3 MLS 1547

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