Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C35H42N7O4.CH3O3S |
| Molecular Weight | 719.85 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CS([O-])(=O)=O.CCC(C)OC(=O)OC[N+]1(C)CCN(CC2=CC=C(C=C2)C(=O)NC3=CC=C(C)C(NC4=NC=CC(=N4)C5=CC=CN=C5)=C3)CC1
InChI
InChIKey=AHMIHOJUHMAHFF-UHFFFAOYSA-N
InChI=1S/C35H41N7O4.CH4O3S/c1-5-26(3)46-35(44)45-24-42(4)19-17-41(18-20-42)23-27-9-11-28(12-10-27)33(43)38-30-13-8-25(2)32(21-30)40-34-37-16-14-31(39-34)29-7-6-15-36-22-29;1-5(2,3)4/h6-16,21-22,26H,5,17-20,23-24H2,1-4H3,(H-,37,38,39,40,43);1H3,(H,2,3,4)
| Molecular Formula | CH3O3S |
| Molecular Weight | 95.098 |
| Charge | -1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C35H42N7O4 |
| Molecular Weight | 624.7525 |
| Charge | 1 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
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
PubMed
| Title | Date | PubMed |
|---|---|---|
| Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia. | 2001 |
|
| Sarcoma. | 2001 |
|
| ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy. | 2001 Aug |
|
| Targeting protein kinases for tumor therapy. | 2001 Aug |
|
| PDGF-beta receptor expression in the dorsocaudal brainstem parallels hypoxic ventilatory depression in the developing rat. | 2001 Aug |
|
| Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. | 2001 Aug 1 |
|
| STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. | 2001 Aug 16 |
|
| Cutaneous reactions to STI571. | 2001 Aug 23 |
|
| [New target-aimed molecular cancer treatment of chronic myeloid leukemia and gastrointestinal stromal tumor]. | 2001 Aug 27 |
|
| Bcr-Abl inhibition as a modality of CML therapeutics. | 2001 Aug 31 |
|
| Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients. | 2001 Feb |
|
| Mechanisms of resistance to imatinib (STI571) and prospects for combination with conventional chemotherapeutic agents. | 2001 Feb |
|
| Perspectives on the future of chronic myeloid leukemia treatment. | 2001 Jul |
|
| Implications of imatinib mesylate for hematopoietic stem cell transplantation. | 2001 Jul |
|
| Interferon-alfa-based treatment of chronic myeloid leukemia and implications of signal transduction inhibition. | 2001 Jul |
|
| Molecular studies in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. | 2001 Jul |
|
| Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia. | 2001 Jul |
|
| The role of Bcr-Abl in chronic myeloid leukemia and stem cell biology. | 2001 Jul |
|
| Implications of signal transduction inhibition for the treatment of chronic myeloid leukemia. | 2001 Jul |
|
| Cancer treatment. New drugs, new hope. | 2001 Jul |
|
| [STI571 and gastro intestinal stromal tumors]. | 2001 Jul |
|
| [Anti-tyrosine kinase: the beginning of molecular therapies of cancer and initial results]. | 2001 Jul |
|
| [Leukemogenesis and new therapy development: the example of chronic myelogenous leukemia]. | 2001 Jul |
|
| Chronic myelogenous leukaemia--new therapeutic principles. | 2001 Jul |
|
| New drug targets genetic malfunction in chronic myeloid leukemia. | 2001 Jul 15 |
|
| New-age drug meets resistance. | 2001 Jul 19 |
|
| After 30 years of laboratory work, a quick approval for STI571. | 2001 Jul 4 |
|
| STI571 revolution: can the newer targeted drugs measure up? | 2001 Jul 4 |
|
| From the Food and Drug Administration. | 2001 Jul 4 |
|
| Current treatment approaches for chronic myelogenous leukemia. | 2001 Jul-Aug |
|
| Tyrosine kinase inhibitor STI571 enhances thyroid cancer cell motile response to Hepatocyte Growth Factor. | 2001 Jun 28 |
|
| Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted therapy of cancer. | 2001 Mar |
|
| Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo. | 2001 Nov |
|
| STI571: a magic bullet? | 2001 Oct |
|
| Chronic myeloid leukemia: current treatment options. | 2001 Oct 1 |
|
| Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. | 2001 Oct 12 |
|
| Requirement for Mdm2 in the survival effects of Bcr-Abl and interleukin 3 in hematopoietic cells. | 2001 Oct 15 |
|
| [Chronic myeloid leukemia and tyrosine kinase inhibitors]. | 2001 Sep |
|
| Improving the management of chronic myeloid leukaemia. | 2001 Sep |
|
| [Chronic myelogenous leukemia]. | 2001 Sep |
|
| Pharmacologic inhibition of the Bcr-Abl kinase with STI571: a novel, safe, and effective therapy for chronic myeloid leukemia. | 2001 Sep |
|
| A possible role for STI571 in the treatment of idiopathic myelofibrosis. | 2001 Sep |
|
| Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein. | 2001 Sep |
|
| Cancer in the crosshairs. | 2001 Sep |
|
| Adhesion to fibronectin selectively protects Bcr-Abl+ cells from DNA damage-induced apoptosis. | 2001 Sep 1 |
|
| Cancer treatment in the STI571 era: what will change? | 2001 Sep 15 |
|
| Roots of clinical resistance to STI-571 cancer therapy. | 2001 Sep 21 |
|
| Roots of clinical resistance to STI-571 cancer therapy. | 2001 Sep 21 |
|
| Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation. | 2001 Sep 27 |
|
| Small molecule: large hopes. | 2001 Sep-Oct |
Sample Use Guides
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
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
Edited
Tue Oct 22 05:19:10 UTC 2019
by
admin
on
Tue Oct 22 05:19:10 UTC 2019
|
| Record UNII |
WQJ8L8YJ7U
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Code | English | ||
|
Common Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
FDA ORPHAN DRUG |
591517
Created by
admin on Tue Oct 22 05:19:10 UTC 2019 , Edited by admin on Tue Oct 22 05:19:10 UTC 2019
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