Photopharmacology – Reversible photoswitches
The MCS group has developed the first light-regulated mGluR5 negative allosteric modulators
The MCS group has developed the first light-regulated mGluR5 negative allosteric modulators
The combination of a reversible photocontrolled ligand with illumination that is patterned in space and time can provide a novel degree of control and regulation of biological receptor activity. This method would allow controlling the location and the temporal extension of its activity. When applied in vivo, the use of reversible photoregulation could reduce side effects by targeting receptors located in specific tissues, establishing high precision, personalized drug schedules to patient needs.
In particular, azobenzene photoisomerization can be used to control biological functions. We have obtained diverse azobenzene molecules with light-dependent activity for GPCRs that can be used both in vitro and in vivo. Thus, local administration of a photoswitchable compound combined with localized illumination in the peripheral tissues of rodents or in the brain results in a precise illumination-dependent analgesic effect.
Among them we have obtained negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu5) and azobenzene photoswitchable allosteric modulators of mGlu4 which allow the control of endogenous receptor activity with light and reversible inhibition of persistent pain symptoms by receptor photocontrol in the brain of freely behaving animals.
These compounds could be used to define novel and more precise therapeutic treatments and to study in vivo the physiological roles of the receptors.
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Goudet C, Rovira X, Llebaria A
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Gómez-Santacana X, Dalton JAR, Rovira X, Pin JP, Goudet C, Gorostiza P, Giraldo J, Llebaria A
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Rovira X, Trapero A, Pittolo S, Zussy C, Faucherre A, Jopling C, Giraldo J, Pin JP, Gorostiza P, Goudet C, Llebaria A
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Dalton JAR, Lans I, Rovira X, Malhaire F, Gómez-Santacana X, Pittolo S, Gorostiza P, Llebaria A, Goudet C, Pin JP, Giraldo J
Curr. Neuropharmacol., 2016, 14(5), 441-454
Consejo Superior de Investigaciones Científicas (CSIC), Universitat Autónoma de Barcelona, Fundació Institut de Bioenginyeria de Catalunya (IBEC), Centre National de la Recherche Scientifique (CNRS), Fundació Institució Catalana de Recerca i Estudis Avançats (ICREA)
Rovira X, Harrak Y, Trapero A, González-Bulnes P, Malhaire F, Pin JP, Goudet C, Giraldo J, Llebaria A
ChemMedChem, 2014, 9(12), 2685-2698
Pittolo S, Gómez-Santacana X, Eckelt K, Rovira X, Dalton J, Goudet C, Pin JP, Llobet A, Giraldo J, Llebaria A, Gorostiza P
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Gómez-Santacana X, Rovira X, Dalton JA, Goudet C, Pin JP, Gorostiza P, Giraldo J, Llebaria A
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Dalton JAR, Gómez-Santacana X, Llebaria A, Giraldo J
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