Endocannabinoid System Modulators

Ana Castro

Tenured Scientist CSIC

Lab members

Nadine Jagerovic, PhD Group Leader

Paula Morales, PhD

Lab contact

Institution

Instituto de Química Médica (IQM-CSIC)

Madrid, Spain


Lab webpage

Our projects

Endocannabinoid System Modulators group is focused on the design, synthesis and molecular recognition of drugs involved in the endocannabinoid system (ECS). During the last two decades, ECS, related to the effects of Cannabis sativa, has been presented as an emerging therapeutic target with a physiological importance of great interest. The contributions of the research group are aimed at understanding the molecular basis of both cannabinoid activity and related therapeutic targets. All this is aimed at the development of new compounds that modulate on the endocannabinoid system. The physiological processes in which most phytocannabinoids, endocannabinoids and synthetic cannabinoids participate are mediated by two cannabinoid receptors coupled to the G-protein (CBR), CB1R and CB2R. CB1R is expressed primarily in the central nervous system, while CB2R is found primarily in the immune system. The side effects of cannabinoids have been a growing concern in the field of endocannabinoids. Thus, two orphan G-protein coupled receptors, GPR55 and GPR18, have been proposed as alternative cannabinoid receptors. Non-direct modulation of the endocannabinoid system is another line of research currently being explored, specifically through modulators of PPAR, AMPK or some of the enzymes involved in the kynurenine pathway.

 In this context, the development of new pharmacological approaches to modulate this system offers the opportunity to focus on complex diseases, such as neurodegenerative diseases in order to propose new therapeutic approaches. This research requires a strong collaboration with national and international pharmacologists, biologists and computer experts.

 Our expertise on drug discovery processes together with our background into technology transfer will be shared with the network to support their achievements.

Last publications

Morales P, Jagerovic  N. Antitumor Cannabinoid Chemotypes: Structural Insights. Frontiers in Pharmacology 10, Article 621, 2019. doi.org/10.3389/fphar.2019.00621

Franco R, Villa M, Morales P, Reyes-Resina I, Gutiérrez-Rodríguez A, Jiménez J, Jagerovic N, Martínez-Orgado J, Navarro G. Increased expression of cannabinoid CB2 and serotonin 5-HT1A heteroreceptor complexes in a model of newborn hypoxic-ischemic brain damage. Neuropharmacology 2019, 152, 58–66, 2019. doi: 10.1016/j.neuropharm.2019.02.004.

Sotudeh N, Morales P, Hurst DP, Lynch DL, Reggio PH. Towards A Molecular Understanding of The Cannabinoid Related Orphan Receptor GPR18: A Focus on Its Constitutive Activity. Int. J. Mol. Sci. 20: 2300, 2019. doi.org/10.3390/ijms20092300

Morales P, Reggio PH. CBD: A New Hope? ACS Med. Chem. Lett.10: 694–695, 2019. doi.org/10.1021/acsmedchemlett.9b00127

Aledavood E, Moraes G, Lameira J, Castro A, Luque FJ, Estarellas C. Understanding the Mechanism of Direct Activation of AMP-Kinase: Towards a Fine Allosteric Tuning of the Kinase Activity. Proceedings, 22:12, 2019. doi.org/10.3390/proceedings2019022012

 

Ana Castro

PhD, Tenured Scientist CSIC

Lab members

Nadine Jagerovic, PhD Group Leader

Paula Morales, PhD

Lab contact

Institution

Instituto de Química Médica (IQM-CSIC)

Madrid, Spain


Lab webpage

Our projects

Endocannabinoid System Modulators group is focused on the design, synthesis and molecular recognition of drugs involved in the endocannabinoid system (ECS). During the last two decades, ECS, related to the effects of Cannabis sativa, has been presented as an emerging therapeutic target with a physiological importance of great interest. The contributions of the research group are aimed at understanding the molecular basis of both cannabinoid activity and related therapeutic targets. All this is aimed at the development of new compounds that modulate on the endocannabinoid system. The physiological processes in which most phytocannabinoids, endocannabinoids and synthetic cannabinoids participate are mediated by two cannabinoid receptors coupled to the G-protein (CBR), CB1R and CB2R. CB1R is expressed primarily in the central nervous system, while CB2R is found primarily in the immune system. The side effects of cannabinoids have been a growing concern in the field of endocannabinoids. Thus, two orphan G-protein coupled receptors, GPR55 and GPR18, have been proposed as alternative cannabinoid receptors. Non-direct modulation of the endocannabinoid system is another line of research currently being explored, specifically through modulators of PPAR, AMPK or some of the enzymes involved in the kynurenine pathway.

 In this context, the development of new pharmacological approaches to modulate this system offers the opportunity to focus on complex diseases, such as neurodegenerative diseases in order to propose new therapeutic approaches. This research requires a strong collaboration with national and international pharmacologists, biologists and computer experts.

 Our expertise on drug discovery processes together with our background into technology transfer will be shared with the network to support their achievements.

Last publications

Morales P, Jagerovic  N. Antitumor Cannabinoid Chemotypes: Structural Insights. Frontiers in Pharmacology 10, Article 621, 2019. doi.org/10.3389/fphar.2019.00621

Franco R, Villa M, Morales P, Reyes-Resina I, Gutiérrez-Rodríguez A, Jiménez J, Jagerovic N, Martínez-Orgado J, Navarro G. Increased expression of cannabinoid CB2 and serotonin 5-HT1A heteroreceptor complexes in a model of newborn hypoxic-ischemic brain damage. Neuropharmacology 2019, 152, 58–66, 2019. doi: 10.1016/j.neuropharm.2019.02.004.

Sotudeh N, Morales P, Hurst DP, Lynch DL, Reggio PH. Towards A Molecular Understanding of The Cannabinoid Related Orphan Receptor GPR18: A Focus on Its Constitutive Activity. Int. J. Mol. Sci. 20: 2300, 2019. doi.org/10.3390/ijms20092300

Morales P, Reggio PH. CBD: A New Hope? ACS Med. Chem. Lett.10: 694–695, 2019. doi.org/10.1021/acsmedchemlett.9b00127

Aledavood E, Moraes G, Lameira J, Castro A, Luque FJ, Estarellas C. Understanding the Mechanism of Direct Activation of AMP-Kinase: Towards a Fine Allosteric Tuning of the Kinase Activity. Proceedings, 22:12, 2019. doi.org/10.3390/proceedings2019022012