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A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz, Adam and Znajdek, Katarzyna and Grudzień, Monika and Pawiński, Tomasz and Sulkowska, Joanna I. (2020) A Guide to Targeting the Endocannabinoid System in Drug Design. International Journal of Molecular Sciences, 21 (8). Art. No. 2778. ISSN 1422-0067. PMCID PMC7216112. https://resolver.caltech.edu/CaltechAUTHORS:20200417-130423295

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Abstract

The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.3390/ijms21082778DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216112PubMed CentralArticle
ORCID:
AuthorORCID
Stasiulewicz, Adam0000-0003-3346-5579
Pawiński, Tomasz0000-0001-9110-4312
Sulkowska, Joanna I.0000-0003-2452-0724
Additional Information:© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Received: 16 March 2020; Accepted: 14 April 2020; Published: 16 April 2020. Author Contributions: Conceptualization, A.S. and J.I.S.; writing—original draft preparation, A.S. and K.Z.; writing—review and editing, M.G., T.P., and J.I.S.; funding acquisition, J.I.S. All authors have read and agreed to the published version of the manuscript. This research was funded by European Molecular Biology Organization installation Grant No. 2057 to J.I.S. and YIP EMBO to J.I.S.. The authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
European Molecular Biology Organization (EMBO)2057
Subject Keywords:endocannabinoid system; ECS; CB1; CB2; FAAH; MAGL; molecular target
Issue or Number:8
PubMed Central ID:PMC7216112
Record Number:CaltechAUTHORS:20200417-130423295
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200417-130423295
Official Citation:Stasiulewicz, A.; Znajdek, K.; Grudzień, M.; Pawiński, T.; Sulkowska, A.J.I. A Guide to Targeting the Endocannabinoid System in Drug Design. Int. J. Mol. Sci. 2020, 21, 2778
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102603
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Apr 2020 21:03
Last Modified:26 May 2020 16:15

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