The journey to imatinib's discovery began with the understanding of the molecular basis of CML. The Philadelphia chromosome was identified in 1960, but it wasn't until the 1980s that researchers discovered that this chromosomal abnormality led to the production of the BCR-ABL fusion protein. This protein has constitutive kinase activity, driving the uncontrolled proliferation of leukemic cells. Researchers hypothesized that inhibiting this abnormal kinase activity could halt the progression of CML. After extensive screening and optimization, imatinib emerged as a potent inhibitor of the BCR-ABL kinase. In 1998, clinical trials began, and the results were promising.
