Introduction
An orphan GPCR offers no validated ligand and no reference pharmacology, so assays have to be built and validated without the usual reference compound. This Masterclass sets out a practical, membrane-based workflow for that situation. It moves from expression and construct design, using HEK293 membranes and NanoLuc fusions, to ThermoBRET thermal-shift measurements that confirm receptor integrity and detect ligand engagement.
It then covers membrane-based G protein recruitment and Gi-CASE assays that read out compound activity, potency, and efficacy. The emphasis throughout is on assay design, controls, and interpretation that transfer directly to other targets. Intended for GPCR scientists and drug discovery professionals working with poorly characterised or orphan receptors.
Instructor
Dmitry Veprintsev studies the structural and biophysical pharmacology of GPCRs, with a focus on how ligands bind and signal at challenging and orphan targets. He is Full Professor of Molecular and Cellular Pharmacology at the Centre of Membrane Proteins and Receptors (COMPARE), University of Nottingham, and co-founder of Z7 Biotech, which applies precision GPCR pharmacology to early-stage discovery.
He previously led a research group at the Paul Scherrer Institute and lectured at ETH Zürich, following earlier work on the tumour suppressor p53 at the MRC LMB in Cambridge. He has authored over 100 papers and collaborates with partners such as Roche on cannabinoid receptor drug discovery.
His Masterclass brings the membrane-based assays he and his colleagues have published, including ThermoBRET and Gi-CASE, to orphan receptor work at Dr. Â GPCR University.