药物化学已发现数千种有效的蛋白质和脂质激酶抑制剂。这些可以开发成治疗药物或化学探针来研究激酶生物学。由于多药理学的原因，目前人类激酶组的很大一部分缺乏选择性化学探针。为了发现此类探针，我们使用 Kinobeads 在癌细胞系裂解物中分析了药物发现项目中的 1,183 种化合物。 ProteomicsDB 中提供了由此产生的 500,000 个化合物-靶点相互作用，我们举例说明了如何使用该分子资源。例如，数据揭示了 72 种激酶的数百种合理选择性化合物。细胞测定验证了 GSK986310C 作为候选 SYK（脾酪氨酸激酶）探针，X 射线晶体学揭示了所观察到的 CK2 抑制剂 GW869516X 选择性的结构基础。发现了针对 PKN3 的化合物，并且磷酸蛋白质组学鉴定了表明细胞中靶标参与的底物。我们预计该分子资源将有助于药物发现和化学生物学的研究。© 2023。作者。

Medicinal chemistry has discovered thousands of potent protein and lipid kinase inhibitors. These may be developed into therapeutic drugs or chemical probes to study kinase biology. Because of polypharmacology, a large part of the human kinome currently lacks selective chemical probes. To discover such probes, we profiled 1,183 compounds from drug discovery projects in lysates of cancer cell lines using Kinobeads. The resulting 500,000 compound-target interactions are available in ProteomicsDB and we exemplify how this molecular resource may be used. For instance, the data revealed several hundred reasonably selective compounds for 72 kinases. Cellular assays validated GSK986310C as a candidate SYK (spleen tyrosine kinase) probe and X-ray crystallography uncovered the structural basis for the observed selectivity of the CK2 inhibitor GW869516X. Compounds targeting PKN3 were discovered and phosphoproteomics identified substrates that indicate target engagement in cells. We anticipate that this molecular resource will aid research in drug discovery and chemical biology.© 2023. The Author(s).