Aditi Shrivastav, Ankita Parihar, Himani Gupta, Neetu Singh, Sudha Srivastava
Department of Biotechnology, JIIT University Noida.
Leukemia is an ever increasing worldwide problem causing death every ten minutes. Chronic myeloid leukemia (CML) represents about 14% of all occurrences of leukemias. Imatinib is the main treatment regimen for patients suffering from CML. Resistance to Imatinib drug in CML patients is increasing at an alarming rate globally. This has been attributed to point mutations in ABL kinase domain of BCR-ABL gene that results in reactivation of BCR-ABL tyrosine kinase leading to abnormal growth of WBC’s and hence CML. Efforts are on to design newer drugs which will remain effective for a wide range of point mutations in BCR-ABL gene. Drugs such as Nilotinib, Dasatinib have been designed, which work by binding to the ATP binding site of BCR-ABL tyrosine kinase, could overcome the resistance (caused by most of the mutations) towards Imatinib. Point mutation at 315 position from Threonine to Isoleucine (T315I) has been the most difficult one to overcome. So far no drug is known to overcome resistance caused by this. Docking studies of the known drugs and drug like molecules (ZINC database) with the BCR-ABL kinase domain with T315I point mutation were carried out in our laboratory and promising results were obtained for ZN0383870 molecule. Read more…