What is the mechanism of imatinib?
Mechanism of Action Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the bcr-abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML).
Which mechanism of action for imatinib makes it effective in treating chronic myelogenous leukemia?
Imatinib inhibits proliferation and induces apoptosis in cells positive for BCR/ABL. For patients with chronic-phase CML, imatinib at 400 mg/day is the best dosage for primary therapy, because it induces a complete hematologic response in almost all patients and causes a high cytogenetic response rate.
What is the target of imatinib?
Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT.
How does imatinib interrupt the activity of the BCR-ABL tyrosine kinase fusion protein?
Imatinib (STI571) is the first drug of Bcr-Abl tyrosine kinase inhibitors that prevents ATP from binding by itself binding to Abl domain via six hydrogen bond interactions [14].
How does imatinib work in CML?
A medicine called imatinib is now the main treatment for CML. It’s usually given soon after a diagnosis is made to slow the progression of the cancer and stop it reaching an advanced phase. Imatinib works by reducing the production of abnormal white blood cells. It’s taken as a tablet once a day.
What type of inhibitor is imatinib?
Imatinib is a member of the class of small molecule tyrosine kinase inhibitors with selectivity for the Abl kinase. Imatinib is a potent competitive inhibitor of ATP binding to Abl kinase, as well as to the c-Kit and PDGF receptor tyrosine kinases.
How does imatinib inhibit BCR-ABL?
Imatinib binds to Abl domain via six hydrogen bond interactions. This stabilizes the imatinib Bcr-Abl complex and prevents ATP from reaching its binding site.
Does imatinib inhibit ABL?
Imatinib, which is an inhibitor of the BCR-ABL tyrosine kinase, has been a remarkable success for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemias (CMLs).
What does tyrosine kinase do in CML?
TKIs are a type of targeted therapy. They work by switching off (inhibiting) the tyrosine kinase made by the BCR-ABL1 gene in leukaemia cells. This slows or stops the bone marrow from making abnormal white blood cells. It also allows the leukaemia cells to mature and die.
Where does imatinib bind to the enzyme?
We have determined the crystal structure of the complex of imatinib with human NQO2 at 1.75 Å resolution, which reveals that imatinib binds in the enzyme active site, adjacent to the flavin isoalloxazine ring.