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Custom Vector Construction> | The genes were synthesized and cloned into the expression vector pGEX6P containing a N-terminal GST tag by GenScript USA Inc... The genes were synthesized and cloned into the expression vector pQE80L containing a N-terminal His6 tag by GenScript USA Inc... JH3 peptide (5FAM-TATKSGSTTKNRFVV-NH2, supplied by GenScript) was used for MNK1 and MNK2 assay.... and ATP were 1.5 nM and 12 µM. FL-peptide 2 (5FAM-EAIYAAPFAKKK-NH2, supplied by GenScript) was used for BCR-ABL1 and ABL T315I assay. | Get A Quote |
Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure-activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiat... More