Feb. 11, 2019 / PRZen
/ DANA POINT, Calif. -- A new article in the Journal of Medicinal Chemistry
describes the characterization of novel selective serotonin 5-HT1A
receptor biased agonists. These compounds preferentially activate a cellular response associated with antidepressant activity (phosphorylation of ERK enzyme), rather than other signaling pathways (adenylyl cyclase, beta-arrestin or calcium release). Such a profile has been previously shown to elicit superior activity in animal models of depression.
The novel compounds (described in patent application WO/2017/220799
) are part of a drug discovery program built on Neurolixis' expertise in biased agonism and conducted in collaboration with scientists at Jagiellonian University (Krakow, Poland). The lead compound in the new series, NLX-204, exhibits potent 5-HT1A
receptor-mediated activation of ERK phosphorylation, favorable pharmacokinetic properties and efficacious antidepressant-like properties in vivo
. Future studies will focus on further development of these compounds for evaluation in man.
Dr. Adrian Newman-Tancredi (CSO of Neurolixis) commented: "Depression constitutes a major healthcare challenge because current antidepressant drugs have multiple activities, are only partially efficacious and take weeks to work. We are excited to have identified highly-selective compounds targeting a signaling pathway associated with rapid antidepressant activity. This opens the way for development of a new generation of drugs offering improved and rapid therapy of depressive disorders."
Neurolixis intends to advance the compounds through preclinical and clinical development by way of licensing or partnering agreements.Novel aryloxyethyl derivatives of 1-(1-benzoylpiperidin-4-yl)methanamine as the Extracellular Regulated Kinases 1/2 (ERK1/2) phosphorylation-preferring serotonin 5HT1A receptor biased agonists with robust antidepressant-like activity.
Sniecikowska J, Guch-Lutwin M, Bucki A, Wickowska A, Siwek A, Jastrzbska-Wisek M, Partyka A, Wilczyska D, Pytka K, Pociecha K, Cios A, Wyska E, Wesoowska A, Pawowski MH, Varney M, Newman-Tancredi A, Koaczkowski M.Journal Medicinal Chemistry
2019 Feb 5. doi: 10.1021/acs.jmedchem.9b00062. PMID: 30721053About Neurolixis, Inc.
Neurolixis, located in Dana Point, California, is a privately held biotechnology company developing therapies for disorders of the central nervous system. The Company is focused on developing small molecule drugs for the treatment of neurological disorders such as Parkinson's disease and Rett syndrome, and of psychiatric disorders such as depression and schizophrenia. Additional information is available at http://www.neurolixis.com
.About Jagiellonian University
Jagiellonian University in Krakw was positioned by QS World University Rankings as the best Polish university among the world's top 500. It is one of the oldest universities in the world (founded in 1364) and is highly reputed in the fields of pharmacy and pharmaceutical sciences (ranked 50-75 in Shanghai Ranking's Global Ranking of Academic Subjects 2018 - Pharmacy & Pharmaceutical Science
). Additional information regarding Jagiellonian University is available athttps://en.uj.edu.pl/enForward Looking Statement
Except for the historical information contained herein, the matters discussed in this press release are forward-looking statements that involve risks and uncertainties, including: our dependence on third parties for the development, regulatory approval and successful commercialization of our products, the inherent risk of failure in developing product candidates based on new technologies, risks associated with the costs of clinical development efforts, as well as other risks. Actual results may differ materially from those projected. These forward-looking statements represent our judgment as of the date of the release. Neurolixis disclaims any intent or obligation to update these forward-looking statements.
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