Sandbox Reserved 425: Difference between revisions
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Potatinib was developed as a treatment option for chronic myeloid leukemia (CML) as other inhibitors in treatment have become ineffective. Further mutations in BCR-ABL, a kinase with a cancerous genetic mutation in chromosome 22 that leaves it always active, has left earlier versions of tyrosine kinases unable to bind in almost 30% of cases over a course of 5 years of treatment. The mutant BCR-ABL kinase’s ability to develop new mutations has pushed for newer developments in inhibitiors like Potatinib [7]. | Potatinib was developed as a treatment option for chronic myeloid leukemia (CML) as other inhibitors in treatment have become ineffective. Further mutations in BCR-ABL, a kinase with a cancerous genetic mutation in chromosome 22 that leaves it always active, has left earlier versions of tyrosine kinases unable to bind in almost 30% of cases over a course of 5 years of treatment. The mutant BCR-ABL kinase’s ability to develop new mutations has pushed for newer developments in inhibitiors like Potatinib [7]. | ||
Fibroblast growth factor (FGFR) signaling, the factor that normally activates the BCR-ABL kinase, is the protein behind both tissue development and repair. The activation happens through a series of cascading signals that induce proliferation and migration in cells. Though mutations in the regulation of the FGFR tyrosine kinase family can result in malignant tumor growth [1]. The tyrosine kinase inhibitor Ponatinib has been used to bind to the mutant version of kinase BCR-ABL by the kinase's specific "DFG-out" conformation. The "DFG-out" 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" combination [1]. | Fibroblast growth factor (FGFR) signaling, the factor that normally activates the BCR-ABL kinase, is the protein behind both tissue development and repair. The activation happens through a series of cascading signals that induce proliferation and migration in cells. Though mutations in the regulation of the FGFR tyrosine kinase family can result in malignant tumor growth [1]. 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 kinase's specific "DFG-out" conformation. The "DFG-out" 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" combination [1]. | |||
The side effects of have caused Ponatinib to fall under scrutiny from the U.S. Food and Drug Administration (FDA). Ponatinib has shown to increase chances of deadly blood clotting and restenosis in both arteries and veins with a rate of about 1 in 5 patients. The drug has also shown to increase risk of heart attack and overall worsening of heart disease in patients [7]. | The side effects of have caused Ponatinib to fall under scrutiny from the U.S. Food and Drug Administration (FDA). Ponatinib has shown to increase chances of deadly blood clotting and restenosis in both arteries and veins with a rate of about 1 in 5 patients. The drug has also shown to increase risk of heart attack and overall worsening of heart disease in patients [7]. | ||
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[[Image:StructureP.PNG]] | [[Image:StructureP.PNG]] | ||
==Binding Interactions== | ==Binding Interactions== | ||
