Fig. 1: Linker-free AATacs mediate the degradation of EML4-ALK.
From: Linker-free PROTACs efficiently induce the degradation of oncoproteins
A The schematic designs of Pro-BA, Gly-BA and Arg-BA. B H3122 cells were exposed to Pro-BA, Gly-BA, or Arg-BA at the specified concentrations for 48 h, and protein levels of EML4-ALK and GAPDH were assessed by immunoblotting. C H3122 cells were separately treated with Pro-BA or Gly-BA at the indicated concentration for 24 h, followed by immunoblot analysis of EML4-ALK and GAPDH protein expression (left panel). The plots were utilized to determine the half-maximal degradation concentration (DC50) values by quantifying EML4-ALK protein levels (right panel). D Summary of DC50 values—defined as the drug concentration resulting in 50% protein degradation, Dmax values—defined as the maximum degradation percentage relative to control, IC50 values—defined as the half maximal inhibitory concentration, and T1/2 values- defined as the time leading to 50% protein degradation for Pro-BA and Gly-BA. E H3122 cell viability was determined utilizing CCK-8 assays after 48 h of treatment with different concentrations of Pro-BA and Gly-BA. F Immunoblot analysis was performed on H3122 cells treated with 250 nM Pro-BA or Gly-BA for different time intervals (left panel). The curves were analyzed to calculate T1/2 values based on the quantification of EML4-ALK protein levels (right panel). G Quantitative proteomics analysis in H3122 cells after treatment with DMSO or 500 nM Pro-BA for 12 h. Data are presented as the log2 fold change (FC) in protein abundance (x-axis) versus the -log10 adjusted p value (y-axis) for each protein, derived from quadruplicate experiments. Two-sided moderated t-test p values were calculated using the LIMMA package, and the horizontal line represents an adjusted p value threshold of 0.05. For (C), (E), (F), the data are shown as mean ± SD derived from three independent experiments. Source data are provided as a Source Data file.
