Sandbox Reserved 425: Difference between revisions

Potatinib was developed as a treatment option for chronic myeloid leukemia (CML) as other inhibitors in treatment have become ineffective. BCR-ABL is a kinase with a cancerous genetic mutation in chromosome 22 that leaves it always active. Further mutations in BCR-ABL have left earlier drugs that inhibit tyrosine kinases unable to bind in almost 30% of cases after five years of treatment. The newer, mutant BCR-ABL kinase’s ability to develop new resistances has pushed for newer developments in inhibitors, such as Potatinib<ref name="seven">PMID: 21118377 </ref>.  

Fibroblast growth factor (FGFR) signaling is the factor that normally activates the BCR-ABL kinase. Also, it is the protein behind both tissue development and repair, the disruption of FGFR leads to tumor growth. The activation of BCR-ABL happens through a series of cascading signals that induce proliferation and migration in cells. Mutations in the regulation of the FGFR tyrosine kinases can be diresctly correlated to malignant tumor growth<ref name="one" />. The tyrosine kinase inhibitor Ponatinib has been used to <scene name='48/483882/Activation_loop/1'>bind</scene> to the mutant version of kinase BCR-ABL by the enzyme's specific "DFG-out" conformation (in <font color='turquoise'><b>turquoise</b></font>). This conformation has the phenylalanine group of BCR-ABL flipped out of its hydrophobic binding site. Ponatinib is the first of its kind to be able to inhibit this specific mutation in BCR-ABL of the "DGF-out" conformation<ref name="seven">PMID: 21118377 </ref>.