Imatinib mesylate CAS 220127-57-1

Introduction：Basic information about Imatinib mesylate CAS 220127-57-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Imatinib mesylate Basic information

• Product Name: Imatinib mesylate
• Synonyms: 4-[(4-methyl-1-piperazinyl)methyl]-n-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate;STI-571;IMATINIB BASE(IMA-3);ImatinibMesylate/Gleevec;Imatinib Methanesulfonate, STI-571, CGP-57148B, Glivec,;IMATINIB MESYLATE (IMATINIB METHANESULFONATE);alpha-IMATINIB MESYLATE;Imatinib mesylate(TINIBS )
• CAS: 220127-57-1
• MF: C30H35N7O4S
• MW: 589.71
• EINECS: 606-892-3
• Product Categories: Inhibitors;Anticancer;Active Pharmaceutical Ingredients;API;Antineoplastic;Anti-cancer&immunity;Intermediates & Fine Chemicals;Pharmaceuticals;Tyrosine Kinase Inhibitors;Aromatics;Heterocycles;Glivec, CGP-57148B, STI-571
• Mol File: 220127-57-1.mol

Imatinib mesylate Chemical Properties

• Melting point: 214-224°C
• storage temp.: 2-8°C
• solubility: H2O: soluble10mg/mL, clear
• form: White solid
• color: white to beige
• Water Solubility: water: 100mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or water may be stored at -20°C for up to 3 months.
• InChIKey: YLMAHDNUQAMNNX-UHFFFAOYSA-N
• SMILES: C(NC1=CC=C(C)C(NC2=NC=CC(C3=CC=CN=C3)=N2)=C1)(=O)C1=CC=C(CN2CCN(C)CC2)C=C1.CS(O)(=O)=O
• CAS DataBase Reference: 220127-57-1(CAS DataBase Reference)

Safety Information

• Hazard Codes: Xn
• Risk Statements: 22
• WGK Germany: 3
• RTECS: CV5520550
• HS Code: 29350090
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Repr. 2
• Hazardous Substances Data: 220127-57-1(Hazardous Substances Data)

Imatinib mesylate Usage And Synthesis

a small-molecule inhibitor

Imatinib mesylate (also called Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia.
As an inhibitor of PDGFR, imatinib mesylate appears to have utility in the treatment of a variety of dermatological diseases. Imatinib has been reported to be an effective treatment for FIP1L1-PDGFRalpha+ mast cell disease, hypereosinophilic syndrome, and dermatofibrosarcoma protuberans.

Description

In May 2001, the FDA approved imatinib as a new cancer drug after a record reviewtime of just 2.5 months. Imatinib was launched as Gleevec in the US for chronicmyelogenous leukemia (CML) in blast crisis, accelerated phase or chronic phase after interferon-alpha failure. This compound can be prepared by a four step sequence from acondensation of the 1-(3-pyridyl)ethanone with dimethyl formamide dimethylacetal,followed by successive cyclization with the methyl-nitrophenyl guanidine, hydrogenolysisand condensation with the benzoyl chloride of the methylpiperazine. Imatinib is the first ofa new class of anticancer drugs that are specifically designed to target the molecularpathways involved (oncogenic event) in the development of disease. The Brc-Abloncoprotein is a constitutively active tyrosine kinase that causes CML. Imatinib is acompetitive inhibitor of this tyrosine kinase as well as Abl, Kit and the PDGFR kinases Itbinds to the ATP-binding site of the target kinase and prevents the transfer of phosphatefrom ATP to the tyrosine residues of various substrates and consequently blocks theproliferation of the leukemic cells. Phase II studies demonstrated that in chronic phaseCML, over 90% of the patients had their leukocyte counts return to normal and 56% had amajor cytogenic response. No phase III data is currently available. It is clear from theevidence available that imatinib has advantages over IFN-alpha, such as reduced toxicity,more rapid hematological response, higher rate of cytogenic response and oraladministration. The drug is well tolerated, producing few side effects, classified as grade 1nausea, muscle cramps, diarrhea, edema and vomiting. Imatinib is metabolized primarilyby the CYP3A4 enzyme system and drugs capable of modulating this system would beexpected to modify the patient's exposure. Novartis expects to launch imatinib for thetreatment of gastrointestinal stromal tumors in 2002.

Chemical Properties

Off-White Solid

Originator

Novartis (Switzerland)

Uses

A tyrosine kinase inhibitor. Highly specific for BCR-ABL, the enzyme associated with chronic myelogenous leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL)

Uses

Imatinib Mesylate is orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively. Imatinib also known as Gleevec, Glivec, CGP-57148B, STI-571 & Imatinib

Uses

Imatinib Mesylate (STI571) is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively.

Uses

echinocandin antifungal, active against infections with Aspergillus and Candida, inhibits cell wall synthesis

Definition

ChEBI: A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.

Brand name

Gleevec, Glivec

General Description

Imatinib is available in 100- and 400-mg capsules for oraladministration and is indicated for the treatment of CML,gastrointestinal stromal tumors (GIST) that express Kit andacute lymphoplastic leukemia that is positive for thePhiladelphia chromosome.
Bioavailability of the agent is nearly 100% by the oralroute. The agent is highly protein bound and metabolized tothe N-desmethyl derivative by CYP3A4-mediated removalof the piperazinyl methyl group. The resulting metabolite issimilar to the parent in activity. Elimination occurs primarilyin the feces, and the terminal half-life is 18 hours forthe parent and 40 hours of the N-desmethyl metabolite.Resistant forms of the TK are known, which have alteredamino acids that prevent binding. In addition, there may beincreased levels of the kinase itself. The drug is also a substratefor Pgp and an additional efflux transporter known asbreast cancer resistance protein (BCRP), both of which removethe drug from the cell. These transporters are also inhibitedby the agent as well. Severe side effects include ascites,neutropenia, thrombocytopenia, skin rash, andpulmonary edema. Less serious side effects include nausea/vomiting, heartburn, and headache but overall, the agentis better tolerated than most other medications used in treatingthe disease.

Biochem/physiol Actions

Imatinib mesylate is a tyrosine kinase inhibitor with antineoplastic activity. Imatinib is a potent inhibitor of the Bcr-Abl kinase encoded by the bcr-abl oncogene as well as receptor tyrosine kinases encoded by c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Imatinib mesylate inhibition of Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality found in CML decreases proliferation and enhances apoptosis in leukemias CML and ALL. Inhibition of c-kit tyrosine activity inhibits mast-cell and cellular proliferation in those diseases overexpressing c-kit such as gastrointestinal stromal tumor (GIST).

storage

+4°C

References

[1] E BUCHDUNGER. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative.[J]. Cancer research, 1996, 56 1: 100-104.
[2] M. HEINRICH. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor.[J]. Blood, 2000, 96 3 1: 925-932. DOI:10.1182/blood.v96.3.925
[3] M. MORIOKA. Effect of Collagen Type I or Human Fibronectin on Imatinib Cytotoxicity in Oral Squamous Cell Carcinoma[J]. Pharmacology & Pharmacy, 2016, 22 1: 255-263. DOI:10.4236/pp.2016.77032
[4] Assessment of cytotoxicity of imatinib for oral squamous cell carcinoma by a real-time cell analysis system