Nanoscale GPCR pharmacology

Mission: accelerate the rational discovery of new GPCR drugs by in silico prediction of intrinsic efficacy.

Summary: Atomos leverages paradigm-breaking, proprietary, technology to measure for the first time the distribution and activity of distinct GPCR conformations in live cells. The direct measurement of intrinsic GPCR drug efficacy will empower next-generation lead selection and error-free training of neural networks.

The Atomos solution: State-Content Analysis (SCA) is the only scalable method able to directly measure the molecular mechanism of GPCR activation in cellulo. Current technology (NMR, DEER, or single-molecule spectroscopy) relies on purification/reconstitution and is not compatible with high-throughput.

SCA leverages subcellular imaging and computational deconvolution to measure simultaneously i) the abundance of distinct GPCR conformations and ii) their specific activity (i.e. their individual ability to stimulate effector proteins). This allows SCA to unmask the conformation-specific effects of drugs which underpin ensemble-average experiments of drug efficacy.

• SCA is scalable and compatible with high-throughput screening, requiring a minute per condition.

• SCA can be applied to any target GPCR that can be overexpressed as a fusion to a fluorescent tag.

• SCA is compatible with primary and immortalized cell cultures, ensuring targets can be matched to their biologically relevant cell type.

• SCA has a sensitivity that is a billion times higher than conventional GPCR activation assays.