Bumped Kinase Inhibitors Inhibit both <i>Toxoplasma gondii</i> MAPKL1 and CDPK1.

ABSTRACT: A subset of bumped kinase inhibitors (BKIs) has been optimized to inhibit the calcium dependent protein kinase 1 (TgCDPK1; TGGT1_301440) of Toxoplasma gondii and pathogenic Cryptosporidium species. Extensive preclinical development of BKIs has identified BKI-1748 as a highly effective lead compound for toxoplasmosis. Phenotypic and therapeutic effects of BKIs have suggested that BKIs may have targets other than TgCDPK1. The mechanism of BKI-1748 action was further investigated using a forward genetic screen of chemical mutagenesis, selection of BKI-1748 resistant clones, and whole genome sequence analysis. Resistant clones were found to have single nucleotide changes in the ATP binding site of the T. gondii mitogen-activated protein kinase-like 1 gene (

SUBMITTER: Montgomery JA 

PROVIDER: S-EPMC12172689 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature