Imatinib Mesylate (STI571)
(Synonyms: 甲磺酸伊马替尼; STI571 Mesylate; CGP-57148B Mesylate) 目录号 : GC11759
Imatinib Mesylate (STI571)是一种口服生物有效的多靶点抑制剂，对Bcr-Abl，c-Kit和PDGFR的IC50分别为0.6μM，0.1μM 和0.1μM。
Cas No.:220127-57-1
Sample solution is provided at 25 µL, 10mM.
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Imatinib Mesylate (STI571) is an orally bioavailable multi-target inhibitor with IC50 values for Bcr-Abl, c-Kit and PDGFR are 0.6μM, 0.1μM and 0.1μM respectively [1]. Tyrosine kinase Bcr-Abl is present throughout the entire disease process of almost all cases of chronic myeloid leukemia (CML) [2]. Imatinib Mesylate is used to treat chronic myeloid leukemia and gastrointestinal stromal tumors [3].
In vitro, Imatinib Mesylate (10μM) incubated with T cells for 1h, reduced the phosphorylation of Lck, ERK 1/2 and Rb proteins, and decreased the levels of cyclin D3 and activated nuclear transcription factor κB (NF-κB) [4]. Different concentrations of Imatinib Mesylate (10, 100, 1000 and 10000ng/mL) were combined with PRI-2191 to treat human lung adenocarcinoma A549 cells for 96 hours. By comparing the proliferation curves of each group of cells, it was observed that the inhibition of cell proliferation exhibited a cumulative effect, and the two had a synergistic effect [5].
In vivo, Imatinib Mesylate (50mg/kg/day; i.p.) was administered 20 minutes before ischemia modeling in rats with ischemia/reperfusion injury (IRI), significantly increasing the level of interleukin (IL)-10, maintaining the expression of vascular endothelial cells (VEC) stable, and inhibiting pCrkL [6]. Imatinib Mesylate (75mg/kg/day; 19 days; i.p.) combined with the vitamin D3 analog PRI-2191 downregulated the expression of VEGF in the tumor tissues of mice, upregulated p53 and downregulated Bcl-2, and significantly inhibited tumor growth [5].
References:
[1] Buchdunger E, Zimmermann J, Mett H, et al. Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class [retracted in: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):12069.
[2] Druker B J, Sawyers C L, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome[J]. New England Journal of Medicine, 2001, 344(14): 1038-1042.
[3] Tibullo D, Giallongo C, La Cava P, et al. Effects of imatinib mesylate in osteoblastogenesis[J]. Experimental hematology, 2009, 37(4): 461-468.
[4] Dietz A B, Souan L, Knutson G J, et al. Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo[J]. Blood, 2004, 104(4): 1094-1099.
[5] Maj E, Filip-Psurska B, Świtalska M, Kutner A, Wietrzyk J. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model. Int J Mol Sci. 2015 Nov 13;16(11):27191-207.
[6] Tanaka S, Chen-Yoshikawa TF, Kajiwara M, Menju T, Ohata K, Takahashi M, Kondo T, Hijiya K, Motoyama H, Aoyama A, Masuda S, Date H. Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung. Ann Thorac Surg. 2016 Nov;102(5):1717-1724.
Imatinib Mesylate (STI571)是一种口服生物有效的多靶点抑制剂，对Bcr-Abl，c-Kit和PDGFR的IC50分别为0.6μM，0.1μM 和0.1μM [1]。酪氨酸激酶Bcr-Abl存在于几乎所有慢性髓细胞白血病（CML）的整个疾病过程中 [2]。Imatinib Mesylate用于治疗慢性粒细胞白血病和胃肠道间质瘤 [3]。
在体外，Imatinib Mesylate（10μM）处理T细胞1小时，可减少Lck、ERK 1/2和Rb蛋白的磷酸化，并降低细胞周期蛋白D3的水平和活化的核转录因子κB（NF-κB）的含量 [4]。不同浓度的Imatinib Mesylate（10、100、1000和10000ng/mL）与PRI-2191联合使用处理人肺腺癌A549细胞96小时，比较各组细胞的增殖曲线，细胞增殖抑制呈现出累积效应，且两者具有协同作用 [5]。
在体内，Imatinib Mesylate（50mg/kg/d；i.p.）在对缺血/再灌注损伤（IRI）的大鼠进行缺血模型构建前20分钟给予，显著提高了白细胞介素（IL）-10的水平，维持了血管内皮细胞（VEC）的表达稳定，并抑制了pCrkL的活性 [6]。Imatinib Mesylate（75mg/kg/d；i.p.）与维生素D3类似物PRI-2191联合使用持续19天，下调了小鼠肿瘤组织中的VEGF表达，上调了p53，下调了 Bcl-2的表达，并显著抑制了肿瘤生长[5]。
| Cell experiment [1]: | |
Cell lines | A549 cells |
Preparation Method | Tested A549 cells were placed in 96-well flat-bottom plates (Sarstedt, Inc., Newton, NC, USA) at a density of 5 × 103 cells per well 24h before the addition of the test compounds. The cells were incubated for 96h with two different concentrations (10 and 100nM) of PRI-2191 and concurrently with various concentrations of Imatinib Mesylate (10, 100, 1000 and 10,000ng/mL) and other cytostatic drugs (DTX or ID: 0.1, 1, 10, 100ng/mL; CIS: 1, 10, 100, 1000ng/mL). The sulforhodamine B (SRB) assay was performed to evaluate the cytotoxic effect, as described previously. As a result, IC50 (inhibitory concentration 50%), i.e., the dose of the tested compound that inhibited the proliferation of cancer cells by 50%, was calculated for each separate experiment in Cheburator 0.4, Dmitry Nevozhay software. Each compound concentration in a given experiment was tested in triplicate; each experiment was repeated 3–5 times. Ethanol, serving as the solvent of the tested agents, in a dilution corresponding to its highest concentration applied with the tested compounds, did not exert any inhibitory effect on cell proliferation (p > 0.05). |
Reaction Conditions | 10, 100, 1000 and 10,000ng/mL; 96h |
Applications | The proliferation curves of each group of cells were compared. The results showed that the combined use of Imatinib Mesylate and PRI-2191 exhibited a cumulative inhibitory effect on cell proliferation, and there was a synergistic effect between the two. |
| Animal experiment [2]: | |
Animal models | Lewis rats（IRI） |
Preparation Method | Male Lewis rats were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes followed by reperfusion for 120 minutes. Imatinib Mesylate (50mg/kg) and a solvent were administered intraperitoneally 20 minutes before ischemia in the imatinib group and the vehicle group, respectively (n = 7 in each group). After reperfusion, lung function, lung wet to dry weight (W/D) ratio, and histologic findings were obtained. The expression of vascular endothelial cadherin (VEC), the phosphorylation level of CrkL (pCrkL) (an exclusive target of Abl kinases), and the cytokine level were evaluated using lung tissue lysate. The imatinib concentrations of plasma and lungs after reperfusion were measured in this hilar clamp model (n = 7). |
Dosage form | 50mg/kg once; i.p. |
Applications | In the Imatinib Mesylate group, lung function was improved with a lower W/D ratio. Perivascular edema and neutrophil infiltration were ameliorated. The imatinib group demonstrated maintained expression of VEC, inhibition of pCrkL, and a significantly higher level of interleukin (IL)-10. |
References: | |
| Cas No. | 220127-57-1 | SDF | |
| 别名 | 甲磺酸伊马替尼; STI571 Mesylate; CGP-57148B Mesylate | ||
| 化学名 | methanesulfonic acid;4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide | ||
| 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 | ||
| 分子式 | C29H31N7O.CH4SO3 | 分子量 | 589.71 |
| 溶解度 | ≥ 29.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6957 mL | 8.4787 mL | 16.9575 mL |
| 5 mM | 0.3391 mL | 1.6957 mL | 3.3915 mL |
| 10 mM | 0.1696 mL | 0.8479 mL | 1.6957 mL |
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动物数量 | 只 |
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- Purity: >99.50%
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