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Molecular glue degraders make one protein destroy another, but thalidomide analogues and indisulam were found by luck. A systematic screen of chemical libraries against genetically diverse cancer cell lines, published as an open atlas, would map which of the roughly 600 human E3 ligases can be redirected and against which targets.
Molecular glue degraders (thalidomide analogues, indisulam) were discovered serendipitously. Modern discovery pairs a chemical library with degradation readouts (global proteomics, reporter panels) across genetically diverse lines, using E3 ligase knockouts to confirm mechanism. A precompetitive atlas of compound-to-degraded-protein pairs would map which of the roughly 600 human E3 ligases can be redirected and against which classes of target.
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Shares Drugging the 'undruggable' cancer targets, The undruggable drivers, PROTACs & molecular glues (targeted protein degradation).