nlx-204

Description: NLX-204 is a novel and selective agonist of ERK1/2 phosphorylation-preferring serotonin 5 HT1A receptor with pKi pf 10.19. NLX-204 displayed high selectivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein. Preliminary in vivo studies confirmed its promising pharmacokinetic profile. NLX-204 also robustly stimulated ERK1/2 phosphorylation in rat cortex and showed highly potent (MED = 0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test.

References: Sniecikowska J, G?uch-Lutwin M, Bucki A, Wi?ckowska A, Siwek A, Jastrz?bska-Wi?sek M, Partyka A, Wilczy?ska D, Pytka K, Pociecha K, Cios A, WyskaE, Weso?owska A, Paw?owski MH, Varney M, Newman-Tancredi A, Ko?aczkowski M. Novelaryloxyethyl derivatives of 1-(1-benzoylpiperidin-4-yl)methanamine as theExtracellular Regulated Kinases 1/2 (ERK1/2) phosphorylation-preferring serotonin5 HT1A receptor biased agonists with robust antidepressant-like activity. J MedChem. 2019 Feb 5. doi: 10.1021/acs.jmedchem.9b00062.