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Details

Stereochemistry ACHIRAL
Molecular Formula C29H31N7O.CH4O3S
Molecular Weight 589.708
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Imatinib Mesylate

SMILES

CS(O)(=O)=O.CN1CCN(CC2=CC=C(C=C2)C(=O)NC3=CC(NC4=NC(=CC=N4)C5=CC=CN=C5)=C(C)C=C3)CC1

InChI

InChIKey=YLMAHDNUQAMNNX-UHFFFAOYSA-N
InChI=1S/C29H31N7O.CH4O3S/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)

HIDE SMILES / InChI

Description

Imatinib (GLEEVEC®) is a tyrosine kinase inhibitor and antineoplastic agent that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive CML. Imatinib (GLEEVEC®) inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib (GLEEVEC®) inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.025 µM [IC50]
0.1 µM [IC50]
0.1 µM [IC50]
39.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GLEEVEC
Primary
GLEEVEC
Primary
GLEEVEC
Primary
GLEEVEC
Primary
GLEEVEC

Cmax

ValueDoseCo-administeredAnalytePopulation
1.74 mg/L
400 mg single, oral
IMATINIB plasma
Homo sapiens
4478 ng/mL
500 mg 2 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
1907.5 ng/mL
400 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
3508.9 ng/mL
600 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
1907.5 ng/mL
400 mg single, oral
IMATINIB plasma
Homo sapiens
4.82 μg/mL
600 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
4.75 μg/mL
500 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
0.71 μg/mL
600 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens
1.18 μg/mL
500 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
19.9 mg × h/L
400 mg single, oral
IMATINIB plasma
Homo sapiens
174.1 ng × h/mL
500 mg 2 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
38.8 ng × h/mL
400 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
89.9 ng × h/mL
600 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
38.8 μg × h/mL
400 mg single, oral
IMATINIB plasma
Homo sapiens
63.7 μg × h/mL
600 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
97.3 μg × h/mL
500 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
10.1 μg × h/mL
600 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens
19.7 μg × h/mL
500 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
15.8 h
400 mg single, oral
IMATINIB plasma
Homo sapiens
17 h
500 mg 2 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
14.8 h
400 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
15.6 h
600 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
83.3 h
600 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
23.6 h
500 mg 2 times / day multiple, oral
IMATINIB plasma
Homo sapiens
50.8 h
600 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens
10.2 h
500 mg 2 times / day multiple, oral
CGP-74588 plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
4%
500 mg 2 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
4%
400 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
4%
600 mg 1 times / day steady-state, oral
IMATINIB plasma
Homo sapiens
5%
400 mg single, oral
IMATINIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The prescribed dose should be administered orally, with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
Route of Administration: Oral
In Vitro Use Guide
Imatinib (CGP 57148) was tested for growth inhibition of EGF-dependent BALB/MK cells, the H-ras-transformed T24 bladder carcinoma line, and IL-3-dependent growth of FDC-Pl cells. The compound showed only weak antiproliferative activity against these cell lines, with IC50 values of 12.7 uM, 9.4 uM, and 29.2 uM, respectively. However, when tested on v-abl-transformed PB-3c cells, incubation with CGP 57148 resulted in potent growth inhibition even in the presence of exogenous IL-3 (IC50 values, 0.11 uM without IL-3 and 0.9 uM with IL-3). Similar results were obtained using v-sis-transformed BALB/c 3T3 cells, which grow in response to autocrine PDGF production (IC50, 0.33 uM).