Fig. 2. Leishmania CDK12 inhibitors and chemical probes from a pyrazolopyrimidine series used in the proteomics MS-based target profiling and mode of action studies.68 Compound 1 (known as DDD853651 or GSK3186899) is a preclinical developmental compound against visceral leishmaniasis. 2 is another potent compound with an aminopiperidine amide functionality. Compound 3 carries an isobutyl group and 2-methoxyphenyl group in place of the trifluoropropyl and 2-methylmorpholine groups in compound 1. Compounds 4 to 7 are structurally related pyrazolopyrimidines with polyethylene glycol linkers. The primary amino groups in 4, 6 and 7 were used for immobilising the compounds on magnetic beads, facilitating affinity enrichment of the protein binders of the compounds from SILAC-labelled parasite cell lysates, whereas compounds 5, 2 and 3 were used as in-solution competitive binders of the proteins in the affinity-enrichment experiments.