KL-50 is active against MSH6-deficient GBM cells. (A) MSH6 and MSH2 protein expression in GBM6 and GBM12 PDX transduced with scrambled RNA versus two different guide RNAs for CRISPR knockdown of MSH6. (B) Western blot analysis of DNA DSB markers in GBM6 or GBM12 glioma cultures with and without MSH6 KO. Cultures were treated with 50 µM of TMZ or KL-50 for 5 days. (C) Dose–response curves for TMZ, KL-50, and CCNU treatment of MMR-deficient versus MMR-proficient GBM6 and GBM12 glioma cells. (D) Tabulated IC₅₀ values for dose–response curves shown in panel (B). CCNU = lomustine; GBM = glioblastoma; MMR = mismatch repair; PDX = patient-derived xenograft; TMZ = temozolomide