IMATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H31N7O
Molecular Weight	493.6027
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=KTUFNOKKBVMGRW-UHFFFAOYSA-N

InChI=1S/C29H31N7O/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/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)

HIDE SMILES / InChI

Molecular Formula	C29H31N7O
Molecular Weight	493.6027
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 Target	Pharmacology	Condition	Potency
Platelet-derived growth factor receptor alpha 26	Inhibitor 7464	Hypereosinophilic Syndrome	0.1 µM [IC50]
Bcr/Abl fusion protein 11	Inhibitor 7464	Leukemia, Myelogenous, Chronic, BCR-ABL Positive	0.025 µM [IC50]
Stem cell growth factor receptor 45	Inhibitor 7464	Mastocytosis, Systemic	0.1 µM [IC50]
Platelet-derived growth factor receptor beta 50	Inhibitor 7464	Myelodysplastic-Myeloproliferative Diseases	39.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Mastocytosis, Systemic 5	Primary	Stem cell growth factor receptor	Approved 7888	GLEEVEC
Myelodysplastic-Myeloproliferative Diseases 3	Primary	Platelet-derived growth factor receptor beta	Approved 7888	GLEEVEC
Hypereosinophilic Syndrome 3	Primary	Platelet-derived growth factor receptor alpha	Approved 7888	GLEEVEC
Leukemia, Myelogenous, Chronic, BCR-ABL Positive 30	Primary	Bcr/Abl fusion protein	Approved 7888	GLEEVEC
Precursor Cell Lymphoblastic Leukemia-Lymphoma 16	Primary	Bcr/Abl fusion protein	Approved 7888	GLEEVEC

PubMed

Title	Date	PubMed
Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia.	2001	11549802
Sarcoma.	2001	11524551
ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy.	2001 Aug	11587372
Targeting protein kinases for tumor therapy.	2001 Aug	11574762
PDGF-beta receptor expression in the dorsocaudal brainstem parallels hypoxic ventilatory depression in the developing rat.	2001 Aug	11477209
Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis.	2001 Aug 1	11479215
STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.	2001 Aug 16	11526490
Chronic myelogenous leukemia.	2001 Aug 22-29	11509034
Cutaneous reactions to STI571.	2001 Aug 23	11529225
[New target-aimed molecular cancer treatment of chronic myeloid leukemia and gastrointestinal stromal tumor].	2001 Aug 27	11572056
Bcr-Abl inhibition as a modality of CML therapeutics.	2001 Aug 31	11553417
Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients.	2001 Feb	11512149
Mechanisms of resistance to imatinib (STI571) and prospects for combination with conventional chemotherapeutic agents.	2001 Feb	11512148
Perspectives on the future of chronic myeloid leukemia treatment.	2001 Jul	11526600
Implications of imatinib mesylate for hematopoietic stem cell transplantation.	2001 Jul	11526599
Interferon-alfa-based treatment of chronic myeloid leukemia and implications of signal transduction inhibition.	2001 Jul	11526598
Molecular studies in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.	2001 Jul	11526597
Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia.	2001 Jul	11526596
The role of Bcr-Abl in chronic myeloid leukemia and stem cell biology.	2001 Jul	11526595
Implications of signal transduction inhibition for the treatment of chronic myeloid leukemia.	2001 Jul	11526594
Cancer treatment. New drugs, new hope.	2001 Jul	11511447
Clinical trials referral resource. ST1571.	2001 Jul	11499689
[STI571 and gastro intestinal stromal tumors].	2001 Jul	11495818
[Anti-tyrosine kinase: the beginning of molecular therapies of cancer and initial results].	2001 Jul	11495817
[Leukemogenesis and new therapy development: the example of chronic myelogenous leukemia].	2001 Jul	11495816
Chronic myelogenous leukaemia--new therapeutic principles.	2001 Jul	11454136
New drug targets genetic malfunction in chronic myeloid leukemia.	2001 Jul 15	11471471
New-age drug meets resistance.	2001 Jul 19	11460142
Current treatment approaches for chronic myelogenous leukemia.	2001 Jul-Aug	11504279
Tyrosine kinase inhibitor STI571 enhances thyroid cancer cell motile response to Hepatocyte Growth Factor.	2001 Jun 28	11439348
Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted therapy of cancer.	2001 Mar	11575716
Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.	2001 Nov	11597734
STI571: a magic bullet?	2001 Oct	11576833
Chronic myeloid leukemia: current treatment options.	2001 Oct 1	11567987
Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.	2001 Oct 12	11489902
Requirement for Mdm2 in the survival effects of Bcr-Abl and interleukin 3 in hematopoietic cells.	2001 Oct 15	11606405
[Chronic myeloid leukemia and tyrosine kinase inhibitors].	2001 Sep	11599196
Improving the management of chronic myeloid leukaemia.	2001 Sep	11584615
[Chronic myelogenous leukemia].	2001 Sep	11579630
Pharmacologic inhibition of the Bcr-Abl kinase with STI571: a novel, safe, and effective therapy for chronic myeloid leukemia.	2001 Sep	11571715
A possible role for STI571 in the treatment of idiopathic myelofibrosis.	2001 Sep	11559942
Treatment of leukemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI-571.	2001 Sep	11532632
Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein.	2001 Sep	11532349
Cancer in the crosshairs.	2001 Sep	11524965
Adhesion to fibronectin selectively protects Bcr-Abl+ cells from DNA damage-induced apoptosis.	2001 Sep 1	11520804
Cancer treatment in the STI571 era: what will change?	2001 Sep 15	11560965
Roots of clinical resistance to STI-571 cancer therapy.	2001 Sep 21	11569495
Roots of clinical resistance to STI-571 cancer therapy.	2001 Sep 21	11567109
Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation.	2001 Sep 27	11593427
Small molecule: large hopes.	2001 Sep-Oct	11584898

Patents

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).

Substance Class	Chemical Created by `admin` on `Mon Oct 21 20:54:26 UTC 2019` Edited by `admin` on `Mon Oct 21 20:54:26 UTC 2019`
Record UNII	BKJ8M8G5HI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IMATINIB

Official Name

English

IMATINIB [WHO-DD]

Common Name

English

GLAMOX

Brand Name

English

IMATINIB [VANDF]

Common Name

English

IMATINIB [MI]

Common Name

English

IMATINIB [INN]

Common Name

English

BENZAMIDE, 4-((4-METHYL-1-PIPERAZINYL)METHYL)-N-(4-METHYL-3-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINOPHENYL)-

Common Name

English

IMATINIB [EMA EPAR]

Common Name

English

Classification Tree Code System Code

WHO-ATC

L01XE01