Langmead C.J.,Heptares Therapeutics
Methods in Molecular Biology | Year: 2011
The drive to produce safer and more receptor subtype selective drugs has sparked a renewed interest in allosteric modulators of G protein-coupled receptors. The increasing use of functional assays has shown that allosteric ligands are capable of modulating both orthosteric agonist affinity and efficacy, as well as mediating receptor activation in their own right. Such a complex range of behaviours can be difficult to discern from single datasets; this chapter seeks to explain how to use radioligand binding and functional assay datasets in concert to elucidate allosteric modulator mechanism of action. © Springer Science+Business Media, LLC 2011. Source
Heptares Therapeutics | Date: 2013-07-03
Heptares Therapeutics | Date: 2014-04-17
A method of producing a conformational specific binding partner of a GPCR, the method comprising: a) providing a mutant GPCR of a parent GPCR, wherein the mutant GPCR has increased stability in a particular conformation relative to the parent GPCR; b) providing a test compound; c) determining whether the test compound binds to the mutant GPCR when residing in a particular conformation; and d) isolating a test compound that binds to the mutant GPCR when residing in the particular formation. Methods of producing GPCRs with increased stability relative to a parent GPCR are also disclosed.
Heptares Therapeutics | Date: 2015-08-26
The invention relates to mutant G-protein coupled receptors with increased conformational stability, and methods of use thereof. In some aspects, polynucleotides encoding the mutant G-protein coupled receptors are provided. In some aspects, host cells comprising the polynucleotides are provided. In some aspects, the invention relates to crystallized forms of the mutant G-protein coupled receptors, and methods of preparing the same.
Heptares Therapeutics | Date: 2015-11-13
This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula I, where n is 1 or 2; p is 0, 1 or 2; q is 0, 1 or 2; and R