Computationally Guided Design of BCR-ABL Tyrosine Kinase Inhibitors

ABSTRACT 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.