ML 2-23

mL 2-23 (0.01-5 μM; 16 h) reduces the protein levels of BCR-ABL and c-ABL in K562 cells in a concentration-dependent manner, with a stronger degradation effect on BCR-ABL than on c-ABL, while simultaneously decreasing the phosphorylation of CRKL, a downstream substrate of BCR-ABL. It only slightly reduces the viability of K562 cells in WST assays, indicating that the observed protein reduction is not caused by general cytotoxicity under the concentration and treatment time used to evaluate BCR-ABL degradation^[1].
Pretreatment with mL 2-23 (1 μM; 12 h; 30 min pretreatment with 5 μM MG132 (HY-13259)) significantly reverses the mL 2-23-induced degradation of BCR-ABL and c-ABL in K562 cells, indicating that this degradation is proteasome-dependent^[1].
mL 2-23 (5 μM; 16 h) does not significantly affect BCR-ABL mRNA levels in K562 cells, but increases c-ABL mRNA levels, indicating that the reduction in BCR-ABL and c-ABL proteins is not caused by transcriptional downregulation^[1].