Pharmacoperones for misfolded gonadotropin receptors

dc.contributor.authorNewton, Claire L.
dc.contributor.authorAnderson, Ross Calley
dc.contributor.emailclaire.newton@up.ac.zaen_ZA
dc.date.accessioned2018-05-18T08:16:51Z
dc.date.issued2018
dc.description.abstractThe gonadotropin receptors (luteinising hormone receptor; LHR and follicle-stimulating hormone receptor; FSHR) are G protein-coupled receptors (GPCRs) that play an important role in the endocrine control of reproduction. Thus genetic mutations that cause impaired function of these receptors have been implicated in a number of reproductive disorders. Disease-causing genetic mutations in GPCRs frequently result in intracellular retention and degradation of the nascent protein through misfolding and subsequent recognition by cellular quality control machinery. The discovery and development of novel compounds termed pharmacological chaperones (pharmacoperones) that can stabilise misfolded receptors and restore trafficking and plasma membrane expression are therefore of great interest clinically, and promising in vitro data describing the pharmacoperone rescue of a number of intracellularly retained mutant GPCRs has provided a platform for taking these compounds into in vivo trials. Thienopyrimidine small molecule allosteric gonadotropin receptor agonists (Org 42599 and Org 41841) have been demonstrated to have pharmacoperone activity. These compounds can rescue cell surface expression and in many cases, hormone responsiveness, of a range of retained mutant gonadotropin receptors. Should gonadotropin receptor selectivity of these compounds be improved, they could offer therapeutic benefit to subsets of patients suffering from reproductive disorders attributed to defective gonadotropin receptor trafficking.en_ZA
dc.description.departmentImmunologyen_ZA
dc.description.embargo2018-12-01
dc.description.librarianhj2018en_ZA
dc.description.urihttps://www.springer.com/series/164en_ZA
dc.identifier.citationNewton C.L., Anderson R.C. (2017) Pharmacoperones for Misfolded Gonadotropin Receptors. In: Ulloa-Aguirre A., Tao YX. (eds) Targeting Trafficking in Drug Development. Handbook of Experimental Pharmacology, vol 245. Springer, Cham.en_ZA
dc.identifier.issn0171-2004
dc.identifier.other10.1007/164_2017_64
dc.identifier.urihttp://hdl.handle.net/2263/64967
dc.language.isoenen_ZA
dc.publisherSpringeren_ZA
dc.rights© Springer International Publishing AG 2017. The original publication is available at : https://www.springer.com/series/164.en_ZA
dc.subjectThienopyrimidinesen_ZA
dc.subjectPharmacoperonesen_ZA
dc.subjectOrg 43553en_ZA
dc.subjectOrg 42599en_ZA
dc.subjectOrg 41841en_ZA
dc.subjectLuteinising hormone receptor (LHR/LHCGR)en_ZA
dc.subjectIntracellular retentionen_ZA
dc.subjectGonadotropin receptorsen_ZA
dc.subjectFollicle-stimulating hormone receptor (FSHR)en_ZA
dc.subjectG protein-coupled receptor (GPCR)en_ZA
dc.titlePharmacoperones for misfolded gonadotropin receptorsen_ZA
dc.typePostprint Articleen_ZA

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