Drug Detail

Information about Gleevec

Generic Name	Imatinib
IND	STI571
Brand Name (US)	Gleevec
Manufacturer	Novartis
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for GIST
Indications	Front-line therapy for GIST and CML
Overall Strategy	KIT Protein Based
Strategy	Block KIT
Drug Category	KIT/PDGFRA inhibitor

Based on the striking results of phase II clinical trials, Gleevec® was filed for registration and received approval from the European Union (EU), the Food and Drug Administration (FDA) in the United States, and several other countries for the treatment of adult patients with c-Kit (CD117)–positive unresectable and/or metastatic malignant GISTs. Gleevec is also approved in the U.S. (Dec. 19th, 2008) for adjuvant treatment (preventative treatment after surgery to remove a primary tumor). It is also approved for adjuvant treatment in other countries.

Gleevec® is known by several different names:

* Gleevec® in the U.S.
* Glivec® outside the U.S.
* Imatinib Mesylate.
* STI571 when it was in clinical trials (STI stands for Signal Transduction Inhibitor).

Gleevec is a pill that is taken either once or twice daily, depending on the dose.

Gleevec is different from traditional chemotherapy in that it is very selective. Traditional chemotherapy kills all cells that are dividing quickly. This is what causes so many of the side effects of traditional chemotherapy. In addition to the cancer cells, this type of chemotherapy also kills many of the bodies normal cells. Gleevec is much more selective and as a result has fewer side effects. It was designed to block the activity of a mutant type of enzyme (an enzyme is a specific type of protein) that causes Chronic Myeloid Leukemia (CML). This enzyme is called Bcr/Abl. In addition to blocking Bcr/Abl, Gleevec also blocks several other enzymes (enzymes are a type of protein). These are:

* KIT.
* Platelet Derived Growth Factor Receptors (PDGFR-alpha and PDGFR-beta).
* Various forms of the Abl enzymes.

The KIT receptor belongs to a class of receptors called the tyrosine kinase family. It is estimated that the human genome will reveal more than 400 tyrosine kinases . Because Gleevec selectively blocks only a few of these tyrosine kinases, it is both effective and has fewer side effects than traditional chemotherapy.

For normal signal transduction to occur in the KIT receptor, a chemical called ATP (adenosine triphosphate) must bind to a site in the kinase domain of the receptor. Gleevec prevents signal transduction of KIT by binding to this ATP binding site. This prevents the transfer of phosphate groups from ATP and blocks signal transduction in normal and mutated forms of KIT.