IMATINIB MESYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H31N7O.CH4O3S
Molecular Weight	589.708
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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

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

Molecular Formula	CH4O3S
Molecular Weight	96.106
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
Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia.	2001	11549802
Sarcoma.	2001	11524551
STI571: targeting BCR-ABL as therapy for CML.	2001	11423669
The oncologic four-minute mile.	2001	11423668
Recent advances in the molecular and cellular biology of chronic myeloid leukaemia: lessons to be learned from the laboratory.	2001 Apr	11328274
ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy.	2001 Aug	11587372
STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.	2001 Aug 16	11526490
Cutaneous reactions to STI571.	2001 Aug 23	11529225
Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.	2001 Aug 3	11423618
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
Perspectives on the future of chronic myeloid leukemia treatment.	2001 Jul	11526600
Implications of imatinib mesylate for hematopoietic stem cell transplantation.	2001 Jul	11526599
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
Cancer treatment. New drugs, new hope.	2001 Jul	11511447
Clinical trials referral resource. ST1571.	2001 Jul	11499689
[Anti-tyrosine kinase: the beginning of molecular therapies of cancer and initial results].	2001 Jul	11495817
Chronic myelogenous leukaemia--new therapeutic principles.	2001 Jul	11454136
New leukemia drug receives FDA approval.	2001 Jul	11433951
Approval heralds new generation of kinase inhibitors?	2001 Jul	11433254
After 30 years of laboratory work, a quick approval for STI571.	2001 Jul 4	11438558
STI571 revolution: can the newer targeted drugs measure up?	2001 Jul 4	11438556
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
Tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: so far so good?	2001 Jun	11409908
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
Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted therapy of cancer.	2001 Mar	11575716
Novel therapies for chronic myelogenous leukemia.	2001 May	11376866
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
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
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 20:46:32 UTC 2019` Edited by `admin` on `Mon Oct 21 20:46:32 UTC 2019`
Record UNII	8A1O1M485B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IMATINIB MESYLATE

Official Name

English

IMATINIB MESYLATE [USAN]

Common Name

English

IMATINIB METHANE SULFONATE

Common Name

English

IMATINIB METHANESULFONATE

Common Name

English

IMATINIB ACCORD

Brand Name

English

IMATINIB MESILATE [MART.]

Common Name

English

IMATINIB MESILATE

Common Name

English

IMATINIB MESYLATE [ORANGE BOOK]

Common Name

English

IMATINIB MESYLATE [HSDB]

Common Name

English

GLIVEC

Common Name

English

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

Common Name

English

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

Common Name

English

IMATINIB MESYLATE [VANDF]

Common Name

English

IMATINIB MESILATE [JAN]

Common Name

English

IMATINIB MEDAC

Brand Name

English

GLEEVEC

Brand Name

English

STI571

Code

English

IMATINIB METHANESULFONATE [MI]

Common Name

English

IMATINIB MESILATE [WHO-DD]

Common Name

English

STI-571

Code

English

STI 571

Code

English

IMATINIB (AS MESILATE)

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

209005