We developed a robust high-throughput screening (HTS) biochemical assay for covalent inhibitors, addressing challenges in identifying inhibitors for difficult protein targets. During the screening of 1,600 covalent fragments, we encountered common synthesis contaminants, leading to false positives. After re-screening, we identified 15 hits showing time-dependent inhibition. Those hits were subjected to structure-activity relationship (SAR) studies, including re-synthesis and enzymatic testing. Our platform successfully differentiated false positives from true hits, confirming inhibitor efficacy through further characterisation assays such as IC50 shifts, jump dilution, and mode of action studies. This highlights the platform's effectiveness in covalent inhibitor discovery.