Imatinib mesylate

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Description:Imatinib mesylate is the mesylate salt of imatinib, a tyrosine kinase inhibitor with antineoplastic activity. Imatinib binds to an intracellular pocket located within tyrosine kinases (TK), thereby inhibiting ATP binding and preventing phosphorylation and the subsequent activation of growth receptors and their downstream signal transduction pathways. This agent inhibits TK encoded by the bcr-abl oncogene as well as receptor TKs encoded by the c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Imatinib is used for chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome-positive (Ph+) and certain types of gastrointestinal stromal tumors (GIST), systemic mastocytosis, and myelodysplastic syndrome.

Price and Availability

Imatinib mesylate, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 100470Name: Imatinib mesylateCAS#: 220127-57-1 (mesylate)Chemical Formula: C30H35N7O4SExact Mass: Molecular Weight: 589.71Elemental Analysis: C, 61.10; H, 5.98; N, 16.63; O, 10.85; S, 5.44

Related CAS #:220127-57-1 (mesylate)152459-95-5 (free base)

Synonym:CGP 57148; CGP57148; CGP-57148; CGP57148B; CGP-57148B; CGP 57148B; STI571; STI-571; STI 571;Imatinib mesylate; US brand name: Gleevec. Foreign brand name: Glivec

IUPAC/Chemical Name:N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide methanesulfonate

InChi Key:YLMAHDNUQAMNNX-UHFFFAOYSA-N

InChi Code: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)

SMILES Code:O=C(NC1=CC=C(C)C(NC2=NC=CC(C3=CC=CN=C3)=N2)=C1)C4=CC=C(CN5CCN(C)CC5)C=C4.CS(=O)(O)=O

Technical Data

Additional Information

According to http://en.wikipedia.org/wiki/Imatinib, Imatinib was developed in the late 1990s by biochemist Nicholas Lydon, a former researcher for Novartis, oncologist Brian Druker of Oregon Health and Science University (OHSU), and Charles Sawyers of Memorial Sloan-Kettering Cancer Center, who led the clinical trials confirming its efficacy in CML. Important contributions to its development were also made by Carlo Gambacorti-Passerini, a physician scientist at University of Milano Bicocca in Italy, and John Goldman, a hematologist at Hammersmith Hospital in London, UK. Imatinib was developed by rational drug design. After the Philadelphia chromosome mutation and defective bcr-abl protein were discovered, the investigators screened chemical libraries to find a drug that would inhibit that protein. With high-throughput screening, they identified 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib  Gleevec received FDA approval in May 2001. On the same month it made the cover of TIME magazine as the "magic bullet" to cure cancer. Druker, Lydon and Sawyers received the Lasker-DeBakey Clinical Medical Research Award in 2009 for "converting a fatal cancer into a manageable chronic condition". Imatinib is a small molecule kinase inhibitor. Gleevec film-coated tablets contain imatinib mesylate equivalent to 100 mg or 400 mg of imatinib free base. Imatinib mesylate is a white to off-white to brownish or yellowish tinged crystalline powder. Its molecular formula is C29H31N7O •CH4SO3 and its molecular weight is 589.7. Imatinib mesylate is soluble in aqueous buffers ≤ pH 5.5 but is very slightly soluble to insoluble in neutral/alkaline aqueous buffers. In non-aqueous solvents, the drug substance is freely soluble to very slightly soluble in dimethyl sulfoxide, methanol and ethanol, but is insoluble in n-octanol, acetone and acetonitrile. Inactive Ingredients: colloidal silicon dioxide (NF); crospovidone (NF); hydroxypropyl methylcellulose (USP); magnesium stearate (NF); and microcrystalline cellulose (NF). Tablet coating: ferric oxide, red (NF); ferric oxide, yellow (NF); hydroxypropyl methylcellulose (USP); polyethylene glycol (NF) and talc (USP). Mechanism of ActionImatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the bcr-abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib inhibits proliferation and induces apoptosis in bcr-abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. In vivo, imatinib inhibits tumor growth of bcr-abl transfected murine myeloid cells as well as bcr-abl positive leukemia lines derived from CML patients in blast crisis.  Imatinib 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 inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-kit mutation.  

References

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