Molecular target identification, also known as target deconvolution, is an essential part of the drug discovery process for understanding compound mechanism of action and further optimizing series of chemical matter. Capture compound mass spectrometry (CCMS) is an unbiased, proteome-wide approach for the identification of specific-binding protein targets for small molecules of interest. The technology combines medicinal chemistry and in vitro pharmacology, coupled to high resolution proteomics mass spectrometry to isolate and identify target proteins that are responsible for the observed biological response.
Charles River’s proprietary Capture Compounds® are bespoke trifunctional molecules, combining reversible affinity binding and photo-induced covalent cross-linking to selectively bind, capture and isolate specific-binding target proteins for identification by mass spectrometry. This distinct three stage process offers significant advantages over traditional chemoproteomic techniques, such as affinity pull down, including greater sensitivity, higher selectivity and enables in-solution live cell workflows. Uniquely, CCMS allows for the isolation and identification of even low abundant specific binders, directly from the relevant phenotypic assay, to demonstrate target engagement at unprecedented sensitivity. The range of target classes and biological matrices that can be assessed using CCMS is unmatched by any other chemoproteomic technique and includes capture of transmembrane proteins, such as GPCRs and even intracellular targets from within living cells. CCMS can also be used to identify off-target activity (unwanted binding) of lead compounds and shed light on potential mechanisms causing toxicity due to such interactions.
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Company: Charles River Laboratories