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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
Structure of IKT-001PRO

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)

HIDE SMILES / InChI

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 ( + / - )

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

PubMed

PubMed

TitleDatePubMed
Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia.
2001
STI571: targeting BCR-ABL as therapy for CML.
2001
The oncologic four-minute mile.
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
Cutaneous reactions to STI571.
2001 Aug 23
[New target-aimed molecular cancer treatment of chronic myeloid leukemia and gastrointestinal stromal tumor].
2001 Aug 27
Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.
2001 Aug 3
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
Clinical trials referral resource. ST1571.
2001 Jul
[Leukemogenesis and new therapy development: the example of chronic myelogenous leukemia].
2001 Jul
New leukemia drug receives FDA approval.
2001 Jul
Approval heralds new generation of kinase inhibitors?
2001 Jul
Anti-cancer drug success emerges from molecular biology origins.
2001 Jul
New drug targets genetic malfunction in chronic myeloid leukemia.
2001 Jul 15
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
Gastrointestinal stromal tumor workshop.
2001 Jun
ABL-specific tyrosine kinase inhibitor, STI571 in vitro, affects Ph-positive acute lymphoblastic leukemia and chronic myelogenous leukemia in blastic crisis.
2001 Jun
Tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: so far so good?
2001 Jun
Gleevec (STI-571) for chronic myeloid leukemia.
2001 Jun 11
Cancer research. Why some leukemia cells resist STI-571.
2001 Jun 22
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
Treatment of leukemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI-571.
2001 Sep
Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein.
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
Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation.
2001 Sep 27
Small molecule: large hopes.
2001 Sep-Oct
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 Tue Oct 22 05:19:10 UTC 2019
Edited
by admin
on Tue Oct 22 05:19:10 UTC 2019
Record UNII
WQJ8L8YJ7U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IKT-001PRO
Code English
1-SEC-BUTOXYCARBONYLOXYMETHYL-1-METHYL-4-(4-(4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYLCARBAMOYL)-BENZYL)-PIPERAZIN-1-IUM MESYLATE
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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