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Imatinib mesylate
- Iupac Name：methanesulfonic acid;4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
- CAS No.: 220127-57-1
- Molecular Weight：589.715
- Modify Date.: 2022-11-10 15:55
- Introduction: 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.
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1. Names and Identifiers
- 1.1 Name
- Imatinib mesylate
- 1.2 Synonyms
4-[(4-Methyl-1-piperazinyl)methyl]-N-(4-methyl-3-{[4-(3-pyridinyl)-2-pyrimidinyl]amino}phenyl)benzamide methanesulfonate 4-[(4-Methyl-1-piperazinyl)methyl]-N-(4-methyl-3-{[4-(3-pyridinyl)-2-pyrimidinyl]amino}phenyl)benzamide methanesulfonate (1:1) 4-[(4-methyl-1-piperazinyl)methyl]-n-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate 4-[(4-Methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide methanesulfonate 4-[(4-Methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide methanesulfonate (1:1) alpha-IMATINIB MESYLATE Benzamide, 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-, methanesulfonate (1:1) Gleevac GLEEVEC Glivec Imantinib mesylate IMATINIB BASE(IMA-3) Imatinib mesilate Imatinib mesilate (JAN) IMATINIB MESYLATE (IMATINIB METHANESULFONATE) Imatinib mesylate(TINIBS ) Imatinib Methanesulfonate, STI-571, CGP-57148B, Glivec, ImatinibMesylate/Gleevec Methansulfonsäure--4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzolcarboxamid(1:1) MFCD04307699 STI-571
- 1.3 CAS No.
- 220127-57-1
- 1.4 CID
- 123596
- 1.5 EINECS(EC#)
- 606-892-3
- 1.6 Molecular Formula
- C30H35N7O4S (isomer)
- 1.7 Inchi
- 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)
- 1.8 InChkey
- YLMAHDNUQAMNNX-UHFFFAOYSA-N
- 1.9 Canonical Smiles
- CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC=CC(=N4)C5=CN=CC=C5.CS(=O)(=O)O
- 1.10 Isomers Smiles
- CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC=CC(=N4)C5=CN=CC=C5.CS(=O)(=O)O
2. Properties
- 2.1 Density
- 0.858?g/mL?at 25?°C(lit.)
- 2.1 Melting point
- 217-227°C
- 2.1 Boiling point
- 754.9 oC at 760 mmHg
- 2.1 Refractive index
- n20/D 1.401(lit.)
- 2.1 Flash Point
- 410.3 oC
- 2.1 Precise Quality
- 589.24700
- 2.1 PSA
- 149.03000
- 2.1 logP
- 5.19690
- 2.1 Solubility
- H2O: soluble10mg/mL, clear
- 2.2 Appearance
- white crystalline powder .
- 2.3 Storage
- -20°C Freezer
- 2.4 Chemical Properties
- Off-White Solid
- 2.5 Color/Form
- White to off white to brownish or yellowish tinged crystalline powder
- 2.6 Water Solubility
- Soluble in aqueous buffers =
- 2.7 StorageTemp
- 2-8°C
3. Use and Manufacturing
- 3.1 Definition
- ChEBI: A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.
- 3.2 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. Imatinib mesylateSupplier
- 3.3 GHS Classification
- Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 74 companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
H302 (82.43%): Harmful if swallowed [Warning Acute toxicity, oral]
H351 (14.86%): Suspected of causing cancer [Warning Carcinogenicity]
H360 (12.16%): May damage fertility or the unborn child [Danger Reproductive toxicity]
Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.
Precautionary Statement Codes
P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501
- 3.4 Usage
- 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)
4. Safety and Handling
- 4.1 Symbol
- GHS07;
- 4.1 Hazard Codes
- Xn
- 4.1 Signal Word
- Warning
- 4.1 Risk Statements
- 22
- 4.1 Safety Statements
- 22
- 4.1 Exposure Standards and Regulations
- The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl imatinib mesylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392). [
- 4.2 Packing Group
- II
- 4.2 Hazard Class
- 3
- 4.2 Hazard Declaration
- H302
- 4.2 DisposalMethods
- SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.
- 4.3 RIDADR
- UN 1993 3/PG 2
- 4.3 Caution Statement
- P301 + P312 + P330
- 4.3 WGK Germany
- 3
- 4.3 RTECS
- CV5520550
- 4.3 Specification
-
?Imatinib mesylate (CAS NO.220127-57-1), its Synonyms are Benzamide, 4-((4-methyl-1-piperazinyl)methyl)-N-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)-, monomethanesulfonate ; 4-[(4-methylpiperazin-1-yl)methyl]-n-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide methanesulfonate ; 4-[(4-methyl-1-piperazinyl)methyl]-n-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate . It is off-white solid.
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Acute toxicity - Oral, Category 4
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Warning |
| Hazard statement(s) | H302 Harmful if swallowed |
| Precautionary statement(s) | |
| Prevention | P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. |
| Response | P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. |
| Storage | none |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
7. Other Information
- 7.0 Target
- Value
- 7.1 PDGFR (Cell-free assay)
- 100 nM
- 7.2 v-Abl (Cell-free assay)
- 600 nM
- 7.3 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.
- 7.4 Description
- In May 2001, the FDA approved imatinib as a new cancer drug after a record review time of just 2.5 months. Imatinib was launched as Gleevec in the US for chronic myelogenous 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 a condensation of the 1-(3-pyridyl)ethanone with dimethyl formamide dimethylacetal, followed by successive cyclization with the methyl-nitrophenyl guanidine, hydrogenolysis and condensation with the benzoyl chloride of the methylpiperazine. Imatinib is the first of a new class of anticancer drugs that are specifically designed to target the molecular pathways involved (oncogenic event) in the development of disease. The Brc-Abl oncoprotein is a constitutively active tyrosine kinase that causes CML. Imatinib is a competitive inhibitor of this tyrosine kinase as well as Abl, Kit and the PDGFR kinases It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates and consequently blocks the proliferation of the leukemic cells. Phase II studies demonstrated that in chronic phase CML, over 90% of the patients had their leukocyte counts return to normal and 56% had a major cytogenic response. No phase III data is currently available. It is clear from the evidence available that imatinib has advantages over IFN-alpha, such as reduced toxicity, more rapid hematological response, higher rate of cytogenic response and oral administration. The drug is well tolerated, producing few side effects, classified as grade 1 nausea, muscle cramps, diarrhea, edema and vomiting. Imatinib is metabolized primarily by the CYP3A4 enzyme system and drugs capable of modulating this system would be expected to modify the patient's exposure. Novartis expects to launch imatinib for the treatment of gastrointestinal stromal tumors in 2002.
- 7.5 Chemical Properties
- Off-White Solid
- 7.6 Originator
- Novartis (Switzerland)
- 7.7 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)
- 7.8 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
- 7.9 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.
- 7.10 Uses
- echinocandin antifungal, active against infections with Aspergillus and Candida, inhibits cell wall synthesis
- 7.11 Definition
- ChEBI: A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.
- 7.12 Brand name
- Gleevec, Glivec
- 7.13 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.
- 7.14 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).
8. Computational chemical data
- Molecular Weight: 589.715g/mol
- Molecular Formula: C30H35N7O4S
- Compound Is Canonicalized: True
- XLogP3-AA: null
- Exact Mass: 589.24712380
- Monoisotopic Mass: 589.24712380
- Complexity: 799
- Rotatable Bond Count: 7
- Hydrogen Bond Donor Count: 3
- Hydrogen Bond Acceptor Count: 10
- Topological Polar Surface Area: 149
- Heavy Atom Count: 42
- Defined Atom Stereocenter Count: 0
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 2
- CACTVS Substructure Key Fingerprint: AAADcfB7uABAAAAAAAAAAAAAAAAAAAAAAAA8eLECAAAAAAAB9AAAHgQQCAAADAjBngS/0JfIEIKoAzV3dHCCgCk1AqAJ2CE4ZNiIaPLA3dGUJQholALIyacYiACOSAAAAAQCAACQAAAACAQAAAAAAAAAAA==
9. Question & Answer
-
Imatinib mesylate is a novel tyrosine kinase inhibitor and a derivative of phenylpyrimidine. About 95% of patients with chronic myeloid leukemia (CML) are Philadelphia chromosome-positive, that is, the proto-oncogene ABL of chromosome 9 is ectopic to the oncogene of chromosome 22 called the breakpo...
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11. Realated Product Infomation
skype
1YR
