Does Gleevec activate BCR-ABL?

Imatinib (also called Gleevec or STI571) is a small-molecule inhibitor that binds to the kinase domain of BCR-ABL and stabilizes the protein in its closed, inactive conformation (5), thereby inhibiting its activity, and is now a first-line therapy for the majority of chronic myelogenous leukemia (CML) cases because of …

Which leukemia is treatable with Gleevec?

NCI-supported research led to a series of discoveries that resulted in the development of imatinib (Gleevec), a landmark drug that has vastly improved the outcomes of patients with a type of blood cancer called chronic myelogenous leukemia.

Does Gleevec prevent BCR-ABL from stimulating the cell cycle?

Gleevec is designed to specifically bind to and inactivate BCR-ABL, which prevents it from signaling the division of more white blood cells.

How long do you take Gleevec for CML?

Gleevec effectiveness In one clinical study, adults with newly diagnosed CML in the chronic phase took Gleevec for seven years. In this group, 96.6 % of people had a complete response to the drug. This means that no cancerous cells were found in their blood, and they had no symptoms of cancer.

Why is imatinib Gleevec a competitive inhibitor?

The drug Gleevec is designed to be a competitive inhibitor for the runaway protein. When Gleevec binds with the protein, the NH2 terminal rotates drastically compared to the active conformation. The rest of the loop mimics a substrate binding to the enzyme, thereby blocking the enzyme active site.

What kind of inhibitor is Gleevec?

Imatinib mesylate (Gleevec, Glivec, Novartis) is a selective inhibitor of ABL, ARG, KIT, PDGFR, and some oncogenic forms, most notably BCR-ABL. Accelerated approval was initially granted by the Food and Drug Administration (FDA) in 2001 for the treatment of Ph+CML after the failure of IFNα therapy.

Does Gleevec stop leukemia?

Mayfield has the blood cancer chronic myelogenous leukemia (CML), and he was among the first patients with the disease treated with the targeted biologic drug Gleevec. Now new research confirms that the drug has transformed a previously fatal leukemia into a manageable chronic disease for many patients who take it.

How long is treatment with Gleevec?

Optimal duration of therapy is unknown but generally imatinib should be continued for 6–9 months, after which additional tumor shrinkage is usually minor.

How does Gleevec work in CML?

Gleevec, the thin molecule shown here in blue, has a specific shape which blocks the active site of the abnormal protein. By binding to the active site, Gleevec prevents the trigger protein from causing the release the white blood cells and alleviates the symptoms of the disease.

What are the side effects of taking Gleevec?

Upset stomach, nausea/vomiting, diarrhea, headache, muscle/joint pain, muscle cramps, dizziness, blurred vision, or drowsiness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. People using this medication may have serious side effects.

How long can you live on imatinib?

All that’s known is that most patients who have been treated with these drugs, starting in 2001 (or even before), are still alive. One large study of CML patients treated with imatinib (Gleevec®) found that about 90% of them were still alive 5 years after starting treatment.