Preladenant | Potent and selective adenosine A2A antagonist

Preladenant (377727-87-2) is a potent (Ki = 1.1nM) and selective (>1000-fold over other adenosine receptors) adenosine A_2A antagonist.¹ It has shown efficacy in rodent and primate models of Parkinsons disease without inducing dyskinesias and displays antidepressant effects.^1-3 It has been shown that activation of the adenosine A_2A receptor blocks the activation of immune cells and increases the number of regulatory T-cells.^4-6 Currently in clinical trials as combination therapy with pembrolizumab.⁷

References/Citations:

1) Hodgson et al. (2009), Characterization of the potent and selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimodin-5-amine] in rat models of movement disorders and depression; J.Pharmacol.Exp.Ther. 330 294
2) Hodgson et al. (2010), Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders; Exp.Neurol. 225 384
3) Pinna et al. (2016), Antidyskinetic effect of A2A and 5HT1A/B receptor ligands in two animal models of Parkinson’s disease; Mov.Disord. 31 501
4) Beavis et al. (2013), Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors; Proc.Natl.Acad.Sci USA. 110 14711
5) Hatfield and Sitkovsky (2016), A2A adenosine receptor antagonist to weaken the hypoxia-HIF-1a driven immunosuppression and improve immunotherapies of cancer; Curr.Opin.Pharmacol. 29 90
6) Ohta et al. (2016), A metabolic immune checkpoint: adenosine in the tumor microenvironment; Front.Immunol. 7 1
7) NCT03099161