RATIONAL DRUG DESIGNING: SUCCESS STORY OF INTRACELLULAR TARGETED AGENTS IN THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA
Journal Title: Asian J of Pharm Sci & Tech - Year 2014, Vol 4, Issue 3
Abstract
[u][/u] ABSTRACT Chronic myeloid leukemia (CML) is a common hematological malignancy encountered in clinical practice. This malignant disorder, is caused due to defective translocation of genetic segment between chromosome 9 and 22 (Philadelphia chromosome), that constitutively activates different proteins and enzymes and favoring cell division. The fused oncogene bcr-abl encoded Bcr-Abl is a trans membrane receptor-linked tyrosine kinase which is expressed in the leukemic clonal cells, activates many pro-growth and cell survival mechanisms. Novel tyrosine kinase Inhibitors like Imatinib mesylate is the first molecule which has proved its efficacy in many malignant disorders including CML by inhibiting cellular tyrosine kinase enzyme. After arrival of imatinib, other 2nd and 3rd generation tyrosine kinase inhibitors have also been introduced, which find their application in imatinib resistant or intolerant patients. Other intracellular targets like aurora kinase, histone deacetylase, heat shock protein 90, proteosome, that gets activated and acts downstream tyrosine kinase also has been identified and have been targeted with different novel drug molecules for their possible role in this unique disorder. This success story can be exploited for targeting other malignant disorders where these proteins get activated. Key words: Cellular tyrosine kinase, Imatinib mesylate, Aurora kinase, Histone deacetylase, Heat shock protein 90, Proteasome.
Authors and Affiliations
Trupti Rekha Swain, Niranjan Rout, Rabindra kumarJena
Keywords
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