Imatinib mesylate
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MedKoo CAT#: 100470

CAS#: 220127-57-1 (mesylate)

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.


Chemical Structure

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Imatinib mesylate
CAS# 220127-57-1 (mesylate)

Theoretical Analysis

MedKoo Cat#: 100470
Name: Imatinib mesylate
CAS#: 220127-57-1 (mesylate)
Chemical Formula: C30H35N7O4S
Exact Mass:
Molecular Weight: 589.71
Elemental Analysis: C, 61.10; H, 5.98; N, 16.63; O, 10.85; S, 5.44

Price and Availability

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2.0g USD 150.0 Same day
5.0g USD 250.0 Same day
10.0g USD 450.0 Same day
20.0g USD 650.0 Same day
50.0g USD 950.0 Same day
100.0g USD 1650.0 Same day
200.0g USD 2650.0 Same day
500.0g USD 3650.0 2 weeks
1.0kg USD 4950.0 2 weeks
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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

Appearance: white to off-white to brownish or yellowish tinged crystalline powder.

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO at 100 mg/mL; very poorly soluble in ethanol; soluble in water at 200 mg/mL.

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Imatinib Mesylate (STI571 Mesylate) is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
In vitro activity: Furthermore, results showed that imatinib with the dose of 100 μg had the same effect as 25 μg amphotericin B on the viability of L. major promastigotes. In addition, imatinib with the dose of 100 μg had almost the same effect as 25 μg amphotericin B on the viability of L. major amastigotes [Table 1]. Three-way repeated ANOVA measurements showed that both two cyclic forms of parasites (P < 0.001), both different doses of imatinib (P < 0.001), and duration of exposure to imatinib (P < 0.001) were effective on survival percentage of parasite stages. As seen in Table 1, the average survival of amastigotes is significantly higher than promastigotes. Increasing the concentration of imatinib, the percentage of survival has declined, as well as with increasing exposure time, the parasite survival rate has decreased. As a result, it can be stated that the percentage of viability of promastigotes and amastigotes produced reverse ratio with the exposure time and drug dosage. For more investigation, the estimated marginal means for different groups and treatment type were presented in Table 2. Reference: Adv Biomed Res. 2019; 8: 61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839269/
In vivo activity: To translate findings in vivo, this study performed a time-resolved study assessing the effects of imatinib on macrophages and metabolic disease manifestations in HFD-induced obese mice: Reduction of TNFα in peritoneal and liver macrophages occurred most rapidly upon imatinib. Activated peritoneal macrophages are known to have both enhanced glycolysis and mitochondrial oxidation. Metabolic flux as another measure for macrophage activation confirmed altered polarization by lower metabolic oxidation upon imatinib. In the liver, this study was able to localize TNFα in liver macrophages, which decreased over time as shown by lower F4/80 area fraction and CD68 gene expression. Thus, it is conceivable that down-regulation of TNFα by imatinib interrupts the vicious cycle of resident liver macrophage activation and/or bone marrow-derived macrophage recruitment to the liver, subsequently lowering their activation and/or number. Reference: Sci Rep. 2018; 8: 15331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193017/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 59.99 101.73
DMF 10.0 16.96
Ethanol 0.2 0.34
PBS (pH 7.2) 2.0 3.39
Water 75.66 128.3

Preparing Stock Solutions

The following data is based on the product molecular weight 589.71 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Moslehi M, Namdar F, Esmaeilifallah M, Hejazi SH, Sokhanvari F, Siadat AH, Hosseini SM, Iraji F. Evaluation of Different Concentrations of Imatinib on the Viability of Leishmania major: An In Vitro Study. Adv Biomed Res. 2019 Oct 31;8:61. doi: 10.4103/abr.abr_58_19. PMID: 31737578; PMCID: PMC6839269. 2. Yao Z, Zhang J, Zhang B, Liang G, Chen X, Yao F, Xu X, Wu H, He Q, Ding L, Yang B. Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages. Pharmacol Res. 2018 Jul;133:121-131. doi: 10.1016/j.phrs.2018.05.002. Epub 2018 May 3. PMID: 29730267. 3. Tanaka A, Nishikawa H, Noguchi S, Sugiyama D, Morikawa H, Takeuchi Y, Ha D, Shigeta N, Kitawaki T, Maeda Y, Saito T, Shinohara Y, Kameoka Y, Iwaisako K, Monma F, Ohishi K, Karbach J, Jäger E, Sawada K, Katayama N, Takahashi N, Sakaguchi S. Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells. J Exp Med. 2020 Feb 3;217(2):e20191009. doi: 10.1084/jem.20191009. PMID: 31704808; PMCID: PMC7041710. 4. AlAsfoor S, Rohm TV, Bosch AJT, Dervos T, Calabrese D, Matter MS, Weber A, Cavelti-Weder C. Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver. Sci Rep. 2018 Oct 17;8(1):15331. doi: 10.1038/s41598-018-32853-w. PMID: 30333571; PMCID: PMC6193017.
In vitro protocol: 1. Moslehi M, Namdar F, Esmaeilifallah M, Hejazi SH, Sokhanvari F, Siadat AH, Hosseini SM, Iraji F. Evaluation of Different Concentrations of Imatinib on the Viability of Leishmania major: An In Vitro Study. Adv Biomed Res. 2019 Oct 31;8:61. doi: 10.4103/abr.abr_58_19. PMID: 31737578; PMCID: PMC6839269. 2. Yao Z, Zhang J, Zhang B, Liang G, Chen X, Yao F, Xu X, Wu H, He Q, Ding L, Yang B. Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages. Pharmacol Res. 2018 Jul;133:121-131. doi: 10.1016/j.phrs.2018.05.002. Epub 2018 May 3. PMID: 29730267.
In vivo protocol: 1. Tanaka A, Nishikawa H, Noguchi S, Sugiyama D, Morikawa H, Takeuchi Y, Ha D, Shigeta N, Kitawaki T, Maeda Y, Saito T, Shinohara Y, Kameoka Y, Iwaisako K, Monma F, Ohishi K, Karbach J, Jäger E, Sawada K, Katayama N, Takahashi N, Sakaguchi S. Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells. J Exp Med. 2020 Feb 3;217(2):e20191009. doi: 10.1084/jem.20191009. PMID: 31704808; PMCID: PMC7041710. 2. AlAsfoor S, Rohm TV, Bosch AJT, Dervos T, Calabrese D, Matter MS, Weber A, Cavelti-Weder C. Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver. Sci Rep. 2018 Oct 17;8(1):15331. doi: 10.1038/s41598-018-32853-w. PMID: 30333571; PMCID: PMC6193017.

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1: Hughes A, Yong ASM. Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission. Front Immunol. 2017 Apr 24;8:469. doi: 10.3389/fimmu.2017.00469. eCollection 2017. Review. PubMed PMID: 28484463; PubMed Central PMCID: PMC5402174.

2: Nakamura K, Matsubara H, Akagi S, Sarashina T, Ejiri K, Kawakita N, Yoshida M, Miyoshi T, Watanabe A, Nishii N, Ito H. Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension. J Clin Med. 2017 Apr 29;6(5). pii: E48. doi: 10.3390/jcm6050048. Review. PubMed PMID: 28468233.

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4: Lanke G, Lee JH. How best to manage gastrointestinal stromal tumor. World J Clin Oncol. 2017 Apr 10;8(2):135-144. doi: 10.5306/wjco.v8.i2.135. Review. PubMed PMID: 28439494; PubMed Central PMCID: PMC5385434.

5: Somlyai G, Collins TQ, Meuillet EJ, Hitendra P, D'Agostino DP, Boros LG. Structural homologies between phenformin, lipitor and gleevec aim the same metabolic oncotarget in leukemia and melanoma. Oncotarget. 2017 Mar 15. doi: 10.18632/oncotarget.16238. [Epub ahead of print] Review. PubMed PMID: 28418852.

6: Campiotti L, Suter MB, Guasti L, Piazza R, Gambacorti-Passerini C, Grandi AM, Squizzato A. Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis. Eur J Cancer. 2017 May;77:48-56. doi: 10.1016/j.ejca.2017.02.028. Epub 2017 Mar 30. Review. PubMed PMID: 28365527.

7: Poveda A, García Del Muro X, López-Guerrero JA, Cubedo R, Martínez V, Romero I, Serrano C, Valverde C, Martín-Broto J; GEIS (Grupo Español de Investigación en Sarcomas/Spanish Group for Sarcoma Research).. GEIS guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev. 2017 Apr;55:107-119. doi: 10.1016/j.ctrv.2016.11.011. Epub 2017 Mar 2. Review. PubMed PMID: 28351781.

8: Alikian M, Gale RP, Apperley JF, Foroni L. Molecular techniques for the personalised management of patients with chronic myeloid leukaemia. Biomol Detect Quantif. 2017 Feb 14;11:4-20. doi: 10.1016/j.bdq.2017.01.001. eCollection 2017 Mar. Review. PubMed PMID: 28331814; PubMed Central PMCID: PMC5348117.

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10: Damrongwatanasuk R, Fradley MG. Cardiovascular Complications of Targeted Therapies for Chronic Myeloid Leukemia. Curr Treat Options Cardiovasc Med. 2017 Apr;19(4):24. doi: 10.1007/s11936-017-0524-8. Review. PubMed PMID: 28316033.

11: Das L, Gitlin M, Siegartel LR, Makenbaeva D. The value of open access and a patient centric approach to oral oncolytic utilization in the treatment of Chronic Myelogenous Leukemia: A U.S. perspective. Expert Rev Pharmacoecon Outcomes Res. 2017 Apr;17(2):133-140. doi: 10.1080/14737167.2017.1305892. Epub 2017 Mar 22. Review. PubMed PMID: 28287008.

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13: Ramachandran KC, Narayanan G, Nair SG, Thambi SM, Kamala LH, Gopinath P, Sreedharan H. Isodicentric Philadelphia Chromosome: A Rare Chromosomal Aberration in Imatinib-Resistant Chronic Myelogenous Leukemia Patients - Case Report with Review of the Literature. Cytogenet Genome Res. 2016;150(3-4):273-280. doi: 10.1159/000458164. Epub 2017 Mar 3. Review. PubMed PMID: 28253493.

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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 Action
Imatinib 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.