Computationally Guided Design of BCR-ABL Tyrosine Kinase Inhibitors

BCR-ABL tyrosine kinase inhibitors (TKI) are used to treat the chronic myeloid leukemia (CML). Many TKI have been developed as the primary treatment to the CML. Imatinib, a first generation TKI, directly targets BCR-ABL with effective results. As the disease becomes more advanced, patients start to develop resistance to imatinib. Due to this effect it is necessary to generate novel treatments for advanced stage CML. Computational tools can predict new drug candidates to target BCR-ABL. We have designed two new drug candidates with different levels of modification, based on the predicted structure activity relationships with BCR-ABL. These new drug candidates are predicted to have better binding affinities with BCR-ABL than imatinib, which can be more potent treatments of the disease.