Fig. 1

Efficacy of XL102 and its effects on downstream targets of CDK7. A Kinase activity of CDK7 in the presence of XL102 was measured using the LANCE TR-FRET in vitro kinase assay by incubating both CDK7 and XL102 followed by addition of ATP and U-light-MBP peptide substrate. Time-resolved fluorescence (excitation, 320 nm; emission donor, 615 nm; emission acceptor, 665 nm) was monitored by using 2030 multilabel reader Victor5 (PerkinElmer). The IC₅₀ values were derived by fitting a sigmoidal dose–response curve to a plot of assay readout over inhibitor concentration, computed with the Graph Pad Prism. B The pull-down assay using bio-THZ1 show a dose dependent target engagement in AML cells harvested after 3 h of XL102 treatment followed by washing to remove any unbound XL102 (time point-0 h). C XL102 inhibited CTD phosphorylation of conserved residues of RPII in AML cells in dose dependent manner at 6 h and 24 h along with quantification of Western blot data. Results are the mean ± SD of three independent experiments