biostudies-literatureIlles-Toth EBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Councile202202075https://www.ebi.ac.uk/biostudies/studies/S-EPMC9542108biostudies-literatureUnknown61(36)Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.Angewandte Chemie (International ed. in English)Mass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.PMC9542108BB/S019456/1EP/S002979/1EP/R018367/1Clayton BIlles-Toth ERose JHughes JWDannhorn ACooper HJStrittmatter NHale OJSargeant RJones SGoodwin RJAfalseMass Spectrometry Detection and Imaging of a Non-Covalent Protein-Drug Complex in Tissue from Orally Dosed Rats.Here, we demonstrate detection by mass spectrometry of an intact protein-drug complex directly from liver tissue from rats that had been orally dosed with the drug. The protein-drug complex comprised fatty acid binding protein 1, FABP1, non-covalently bound to the small molecule therapeutic bezafibrate. Moreover, we demonstrate spatial mapping of the [FABP1+bezafibrate] complex across a thin section of liver by targeted mass spectrometry imaging. This work is the first demonstration of in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo and has implications for early stage drug discovery by providing a route to target-drug characterization directly from the physiological environment.2022-01-01T00:00:00Z2022 Sep2026-05-28T04:19:51.785Z2024-11-15T00:43:39.188ZS-EPMC95421083583033210.1002/anie.202202075