gsk2018682

Description: GSK2018682 is a novel and potent agonist for S1P1 and S1P5 receptor (sphingosine 1 phosphate receptor) with pEC50s of 7.7 and 7.2, respectively, and it has no agonist activity towards human S1P2, S1P3, or S1P4. GSK2018682 is used in the research of multiple sclerosis. GSK2018682 induced acute, transient and non-symptomatic decreases in heart rate and blood pressure. Dose-dependent reduction in absolute lymphocyte count (ALC), and all tested subsets, was observed to various degrees, up to a nadir of over 70% reduction from baseline. There was no difference in major pharmacokinetic parameters among three formulations of GSK2018682 and between fasted and fed subjects. However, there was a reduction in the extent of bradycardia following dosing in the fed state. Additionally, exercise induced robust increase in heart rate in subjects who had bradycardia following RD of GSK2018682 up to 6?mg, suggesting possible physiological methods of reducing the extent of S1P mediated bradycardia and subsequent AV-block.

References: Clin Pharmacol Drug Dev. 2014 May; 3(3):170-8.