MLS 1547

Names

[ Name ]:
MLS 1547

[Synonym ]:
MLS1547
5-chloro-7-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}quinolin-8-ol
5-Chloro-7-(4-pyridin-2-yl-piperazin-1-ylmethyl)-quinolin-8-ol
5-Chloro-7-{[4-(2-pyridinyl)-1-piperazinyl]methyl}-8-quinolinol
8-Quinolinol, 5-chloro-7-[[4-(2-pyridinyl)-1-piperazinyl]methyl]-
MFCD02330713

Biological Activity

[Description]:

MLS1547 is a highly efficacious G protein-biased dopamine D2 receptor (D2R) agonist (Ki=1.2 μM). MLS1547 stimulates D2R G protein-mediated signaling (EC50=0.37 μM in a calcium mobilization assay). MLS1547 acts as an antagonist for dopamine (DA)-stimulated β-arrestin recruitment to the D2R (IC50=9.9 μM)[1][2].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

[In Vitro]

MLS1547 fully antagonizes dopamine-mediated β-arrestin recruitment to the D2R in the DiscoveRx assay, with an IC50 of 9.9 μM. Similar results were obtained when MLS1547 was examined for antagonist activity in the D2R β-arrestin BRET assay, demonstrating an IC50 of 3.8 μM. MLS1547 is found to completely displace [3H]methylspiperone binding to the D2R, with a calculated Ki of 1.2 μM[1].

[References]

[1]. Free RB, et al. Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor. Mol Pharmacol. 2014;86(1):96-105.

[2]. Chun LS, et al. Structure-Activity Investigation of a G Protein-Biased Agonist Reveals Molecular Determinants for Biased Signaling of the D2 Dopamine Receptor. Front Synaptic Neurosci. 2018;10:2. Published 2018 Feb 21.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
555.8±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₉H₁₉ClN₄O

[ Molecular Weight ]:
354.833

[ Flash Point ]:
289.9±30.1 °C

[ Exact Mass ]:
354.124725

[ LogP ]:
3.19

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.689

[ Storage condition ]:
-20°C

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310 + P330

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor.

Mol. Pharmacol. 86(1) , 96-105, (2014)

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 compoun...