SandboxPKA: Difference between revisions
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== '''Bcr-Abl tyrosine-kinase inhibitors''' == | == '''Bcr-Abl tyrosine-kinase inhibitors''' == | ||
{{STRUCTURE_2hyy| PDB=2hyy | SIZE=350 | SCENE= |right| CAPTION=Human Abl kinase domain in complex with imatinib}} | {{STRUCTURE_2hyy| PDB=2hyy | SIZE=350 | SCENE= |right| CAPTION=Human Abl kinase domain in complex with imatinib}} | ||
=== '''1st Generation TKIs: Gleevec''' === | === '''1st Generation TKIs: Gleevec''' === | ||
[[Image:Imatinib_bound_to_receptor.PNG|thumb|left|Imatinib]] | [[Image:Imatinib_bound_to_receptor.PNG|thumb|left|Imatinib]] | ||
'''[[Imatinib]] mesylate''' ('''STI571''' or '''Gleevec'''), discovered in 1992, is a Bcr-Abl tyrosine kinase inhibitor (Bcr-Abl TKI) and it's the most common first generation drug used for the CML treatment. Imatinib has a high affinity for ABL kinase. | '''[[Imatinib]] mesylate''' ('''STI571''' or '''Gleevec'''), discovered in 1992, is a Bcr-Abl tyrosine kinase inhibitor (Bcr-Abl TKI) and it's the most common first generation drug used for the CML treatment. Imatinib has a high affinity for ABL kinase. | ||
Imatinib achieves BCR-ABL kinase inhibition by binding to the inactive, unphosphorylated conformation of the kinase (DFG-out)</scene> , thereby reducing the availability of the catalytically active phosphorylated conformation (DFG-in), necessary for ATP binding. This blocks signal transduction, ultimately resulting in inhibition of proliferation and loss of viability and proliferation.<ref>Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol. 2006;2:358 – 64.</ref>. | Imatinib achieves BCR-ABL kinase inhibition by binding to the inactive, unphosphorylated conformation of the kinase (DFG-out)</scene> , thereby reducing the availability of the catalytically active phosphorylated conformation (DFG-in), necessary for ATP binding. This blocks signal transduction, ultimately resulting in inhibition of proliferation and loss of viability and proliferation.<ref>Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol. 2006;2:358 – 64.</ref>. | ||
