Name: | imatinib |
---|---|
PubChem Compound ID: | 10435761 |
Molecular formula: | C29H31N7O |
Molecular weight: | 492.604 g/mol |
Name: | imatinib |
---|---|
Name (isomeric): | DB00619 |
Drug Type: | small molecule |
Synonyms: |
Imatinib Methansulfonate; STI-571; Imatinib Mesylate
|
Brand: | Gleevec, Glivec |
Category: | Antineoplastic Agents, Protein Kinase Inhibitors |
CAS number: | 152459-95-5 |
Indication: | For the treatment Philadelphia chromosome positive chronic myeloid leukemia (CML) and malignant gastrointestinal stromal tumors (GIST). |
---|---|
Pharmacology: |
Imatinib is an antineoplastic agent used to treat chronic myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of Abl with Bcr (breakpoint cluster region), termed Bcr...
show more »
Imatinib is an antineoplastic agent used to treat chronic myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of Abl with Bcr (breakpoint cluster region), termed Bcr-Abl. As this is now a continuously active tyrosine kinase, Imatinib is used to decrease Bcr-Abl activity.
show less « |
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). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philad...
show more »
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). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib also inhibits the receptor tyrosine kinases for platelet derived growth factor (PDGF) and stem cell factor (SCF) - called c-kit. Imatinib was identified in the late 1990s by Dr Brian J. Druker. Its development is an excellent example of rational drug design. Soon after identification of the bcr-abl target, the search for an inhibitor began. Chemists used a high-throughput screen of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.
show less « |
Absorption: | Imatinib is well absorbed with mean absolute bioavailability is 98% with maximum levels achieved within 2-4 hours of dosing |
Protein binding: | Very high (95%) |
Biotransformation: | Primarily hepatic via CYP3A4. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. |
Route of elimination: | Imatinib elimination is predominately in the feces, mostly as metabolites. |
Half Life: | 18 hours for Imatinib, 40 hours for its major active metabolite, the N-desmethyl derivative |
Clearance: | 8 L/h [50-year-old CML and GIST patient weighing 50 kg] 14 L/h [50-year-old CML and GIST patient weighing 100 kg] |
Toxicity: | Side effects include nausea, vomiting, diarrhea, loss of appetite, dry skin, hair loss, swelling (especially in the legs or around the eyes) and muscle cramps |
Affected organisms: | Humans and other mammals |
Food interaction: |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Drug interaction: |
|
UniProt ID: | A9UF02 | |||
---|---|---|---|---|
Gene: | BCR/ABL fusion | |||
Actions: | inhibitor | |||
References: |
|
UniProt ID: | P10721 | |||||
---|---|---|---|---|---|---|
Gene: | KIT | |||||
Actions: | antagonist, multitarget | |||||
References: |
|
UniProt ID: | O43519 | |
---|---|---|
Gene: | RET | |
Actions: | inhibitor | |
References: |
|
UniProt ID: | P04629 | |||||
---|---|---|---|---|---|---|
Gene: | NTRK1 | |||||
Actions: | antagonist | |||||
References: |
|
UniProt ID: | P07333 | |||||
---|---|---|---|---|---|---|
Gene: | CSF1R | |||||
Actions: | antagonist | |||||
References: |
|
UniProt ID: | P16234 | |||||
---|---|---|---|---|---|---|
Gene: | PDGFRA | |||||
Actions: | antagonist | |||||
References: |
|
UniProt ID: | Q08345 | |||||
---|---|---|---|---|---|---|
Gene: | DDR1 | |||||
Actions: | antagonist | |||||
References: |
|
UniProt ID: | P00519 | |||||
---|---|---|---|---|---|---|
Gene: | ABL1 | |||||
Actions: | inhibitor | |||||
References: |
|
UniProt ID: | P09619 | |||||
---|---|---|---|---|---|---|
Gene: | PDGFRB | |||||
Actions: | antagonist | |||||
References: |
|
UniProt ID: | P08684 | ||||
---|---|---|---|---|---|
Gene: | CYP3A4 | ||||
Actions: | substrate, inhibitor | ||||
References: |
|
UniProt ID: | P20815 | |||
---|---|---|---|---|
Gene: | CYP3A5 | |||
Actions: | substrate, inhibitor | |||
References: |
|
UniProt ID: | P24462 | |
---|---|---|
Gene: | CYP3A7 | |
Actions: | substrate, inhibitor | |
References: |
|
UniProt ID: | P05177 | |||
---|---|---|---|---|
Gene: | CYP1A2 | |||
Actions: | substrate | |||
References: |
|
UniProt ID: | P11712 | ||
---|---|---|---|
Gene: | CYP2C9 | ||
Actions: | substrate, inhibitor | ||
References: |
|
UniProt ID: | P10635 | ||
---|---|---|---|
Gene: | CYP2D6 | ||
Actions: | substrate, inhibitor | ||
References: |
|
UniProt ID: | P33261 | |
---|---|---|
Gene: | CYP2C19 | |
Actions: | substrate | |
References: |
|
UniProt ID: | P23219 | |
---|---|---|
Gene: | PTGS1 | |
Actions: | substrate | |
References: |
|
UniProt ID: | O15245 | |||
---|---|---|---|---|
Gene: | SLC22A1 | |||
Actions: | substrate, inhibitor | |||
References: |
|
UniProt ID: | P08183 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene: | ABCB1 | |||||||||||
Actions: | substrate, inhibitor | |||||||||||
References: |
|
UniProt ID: | O15244 | ||
---|---|---|---|
Gene: | SLC22A2 | ||
Actions: | inhibitor | ||
References: |
|
UniProt ID: | Q9UNQ0 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene: | ABCG2 | |||||||||||
Actions: | substrate, inhibitor | |||||||||||
References: |
|
UniProt ID: | Q99758 | |
---|---|---|
Gene: | ABCA3 | |
Actions: | substrate | |
References: |
|