6 research outputs found
Identification of Hydroxybenzoic Acids as Selective Lactate Receptor (GPR81) Agonists with Antilipolytic Effects
Following the characterization of the lactate receptor
(GPR81), a focused screening effort afforded 3-hydroxybenzoic acid <b>1</b> as a weak agonist of both GPR81 and GPR109a (niacin receptor).
An examination of structurally similar arylhydroxy acids led to the
identification of 3-chloro-5-hydroxybenzoic acid <b>2</b>, a
selective GPR81 agonist that exhibited favorable in vivo effects on
lipolysis in a mouse model of obesity
Shifting of amidated RXFP3 agonist concentration response curves by 135PAM1 in cells lacking chimeric G proteins.
<p>SK-N-MC cells coexpressing RXFP3 and a reporter construct linking CRE activity to β-galactosidase were incubated with fixed concentrations of 135PAM1 (0, 0.2, 2 and 20 µM) and increasing concentrations of Relaxin-3<sub>NH2</sub> (A) or R3I5<sub>NH2</sub> (B).</p
135PAM1 increases the intracellular Ca<sup>2+</sup> response to amidated, but not free acid RXFP3 agonists in cells coexpressing RXFP3 and G<sub>qI5</sub>.
<p>Intracellular Ca<sup>2+</sup> responses by HEK-293 cells coexpressing RXFP3 and G<sub>qI5</sub> were measured in response to escalating concentrations of 135PAM1 using probe (EC<sub>20</sub>) concentrations of Relaxin-3<sub>NH2</sub> (A), Relaxin-3<sub>OH</sub> (B), R3/I5<sub>NH2</sub> (C), or R3/I5<sub>OH</sub> (D).</p
Structure of 135PAM1 (3-[3,5-Bis(trifluoromethyl)phenyl]-1-(3,4-dichlorobenzyl)-1-[2-(5-methoxy-1H-indol-3-yl)ethyl]urea).
<p>Structure of 135PAM1 (3-[3,5-Bis(trifluoromethyl)phenyl]-1-(3,4-dichlorobenzyl)-1-[2-(5-methoxy-1H-indol-3-yl)ethyl]urea).</p
135PAM1 shifts the concentration response curves of Relaxin-3<sub>NH2</sub> and R3/I5<sub>NH2</sub>.
<p>HEK-293 cells coexpressing RXFP3 and G<sub>qI5</sub> were incubated with fixed concentrations of 135PAM1 (0, 0.2, 2 and 20 µM) 10 min before the addition of increasing concentrations of Relaxin-3<sub>NH2</sub> (A), R3I5<sub>NH2</sub> (B), Relaxin-3<sub>OH</sub> (C) or R3I5<sub>OH</sub> (D).</p
135PAM1 lacks affinity at the orthosteric binding site of RXFP3 receptor.
<p>135PAM1 did not displace [125I] R3/I5<sub>NH2</sub> at concentrations of up to 20 µM, but instead increased total binding. R3/I5<sub>NH2</sub> displaced the tracer with a pIC<sub>50</sub> of 8.76 (8.91 to 8.61).</p