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 7468	Hypereosinophilic Syndrome	0.1 µM [IC50]
Bcr/Abl fusion protein 11	Inhibitor 7468	Leukemia, Myelogenous, Chronic, BCR-ABL Positive	0.025 µM [IC50]
Stem cell growth factor receptor 45	Inhibitor 7468	Mastocytosis, Systemic	0.1 µM [IC50]
Platelet-derived growth factor receptor beta 50	Inhibitor 7468	Myelodysplastic-Myeloproliferative Diseases	39.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Mastocytosis, Systemic 5	Primary	Stem cell growth factor receptor	Approved 7883	GLEEVEC
Myelodysplastic-Myeloproliferative Diseases 3	Primary	Platelet-derived growth factor receptor beta	Approved 7883	GLEEVEC
Hypereosinophilic Syndrome 3	Primary	Platelet-derived growth factor receptor alpha	Approved 7883	GLEEVEC
Leukemia, Myelogenous, Chronic, BCR-ABL Positive 30	Primary	Bcr/Abl fusion protein	Approved 7883	GLEEVEC
Precursor Cell Lymphoblastic Leukemia-Lymphoma 16	Primary	Bcr/Abl fusion protein	Approved 7883	GLEEVEC

PubMed

Title	Date	PubMed
Sarcoma.	2001	11524551
The oncologic four-minute mile.	2001	11423668
Mechanisms of transformation by the BCR/ABL oncogene.	2001 Apr	11345193
Recent advances in the molecular and cellular biology of chronic myeloid leukaemia: lessons to be learned from the laboratory.	2001 Apr	11328274
Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors.	2001 Apr 1	11306470
ARG tyrosine kinase activity is inhibited by STI571.	2001 Apr 15	11290609
Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia.	2001 Apr 5	11287980
Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor.	2001 Apr 5	11287975
Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.	2001 Apr 5	11287973
ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy.	2001 Aug	11587372
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
Chronic myelogenous leukemia.	2001 Aug 22-29	11509034
Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.	2001 Aug 3	11423618
Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients.	2001 Feb	11512149
Molecular studies in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.	2001 Jul	11526597
The role of Bcr-Abl in chronic myeloid leukemia and stem cell biology.	2001 Jul	11526595
Cancer treatment. New drugs, new hope.	2001 Jul	11511447
[STI571 and gastro intestinal stromal tumors].	2001 Jul	11495818
New leukemia drug receives FDA approval.	2001 Jul	11433951
Anti-cancer drug success emerges from molecular biology origins.	2001 Jul	11431023
New drug targets genetic malfunction in chronic myeloid leukemia.	2001 Jul 15	11471471
New-age drug meets resistance.	2001 Jul 19	11460142
After 30 years of laboratory work, a quick approval for STI571.	2001 Jul 4	11438558
From the Food and Drug Administration.	2001 Jul 4	11434814
ABL-specific tyrosine kinase inhibitor, STI571 in vitro, affects Ph-positive acute lymphoblastic leukemia and chronic myelogenous leukemia in blastic crisis.	2001 Jun	11417489
Quick success for cancer kinase treatment.	2001 Jun	11385473
Gleevec (STI-571) for chronic myeloid leukemia.	2001 Jun 11	11402258
Researchers optimistic about sea change in cancer treatment.	2001 Jun 13	11401587
Cancer research. Why some leukemia cells resist STI-571.	2001 Jun 22	11423629
Promising clinical trials on kinase inhibitor.	2001 Mar	11306264
Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease.	2001 Mar	11298594
Chronic myeloid leukaemia. STI 571 magnifies the therapeutic dilemma.	2001 Mar	11290430
Co-treatment with As2O3 enhances selective cytotoxic effects of STI-571 against Brc-Abl-positive acute leukemia cells.	2001 May	11368438
STI571: a gene product-targeted therapy for leukemia.	2001 May	11296132
Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement.	2001 May 1	11291071
Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of retinoic acid in acute promyelocytic leukemia cells: effects on the degradation of RARalpha and PML-RARalpha.	2001 May 15	11342454
Cancer's mechanics. Targeting errant cells.	2001 May 21	11383095
New hope for cancer.	2001 May 28	11393038
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
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
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	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