Masitinib mesylate
(Synonyms: 甲磺酸马赛替尼; AB-1010 mesylate) 目录号 : GC36546
An inhibitor of c-Kit
Cas No.:1048007-93-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | A 96-well microtitre plateis coated overnight with 0.25 mg/mL poly(Glu,Tyr 4:1), rinsed twice with 250 µL of washing buffer (10 mM phosphate-buffered saline [pH 7.4] and 0.05% Tween 20) and dried for 2 hours at room temperature. Assays are performed at room temperature with a final volume of 50 µL in kinase buffer (10 mM MgCl2, 1 mM MnCl2, 1 mM sodium orthovanadate, 20 mM HEPES, pH 7.8) containing ATP at a concentration of at least twice the Km for each enzyme and an appropriate amount of recombinant enzyme to ensure a linear reaction rate. Reactions are initiated upon introduction of the enzyme and terminated with the addition of one reaction volume (50 μL) of 100 mM EDTA per 5mol/Lurea mix. Plates are washed three times and incubated with 1:30,000 horseradish peroxidase-conjugated anti-phosphotyrosine monoclonal antibody, then washed three times and incubated with tetramethylbenzidine. The final reaction product is quantified by spectrophotometry at 450 nm. |
Cell experiment: | For the assay of Ba/F3 cell proliferation, microtitre plates are seeded with a total of 104 cells/well in 100 μL of RPMI 1640 medium with 10% foetal bovine serum at 37°C. These are supplemented, or not, with either 0.1% conditioned medium from X63-IL-3 cells or 250 ng/mL murine SCF. The murine SCF, which activates Kit, is purified from the conditioned medium of SCF-producing CHO cells. Cells are grown for 48 hours at 37°C with masitinib and then incubated with 10 μL/well of WST-1 reagent for 3 hours at 37°C. The amount of formazan dye formed is quantified by its absorbance at 450 nm using a scanning multiwell spectrophotometer. A blank well without cells is used as a background control for the spectrophotometer. |
Animal experiment: | Male Nog-SCID mice (7 weeks old) are under specific pathogen-free conditions at 20±1°C in a 12-hour light/12-hour dark cycle and ad libitum access to food and filtered water. Mia Paca-2 cells are cultured as described above. At day 0 (D0), mice are injected with 107 Mia Paca-2 cells in 200 µL PBS into the right flank. Tumours are allowed to grow for 1.5 to 4 weeks until the desired tumour size is reached (appr 200 mm3). At day 28, animals are allocated into four treatment groups (n=7 to 8 per group), ensuring that each group's mean body weight and tumour volume are well matched. Treatment is then administered for up to 4 weeks, after which time the animals are sacrificed. Treatments consisted of either: a) daily sterile water for the control group, b) an intraperitoneal (i.p.) injection of 50 mg/kg gemcitabine twice a week, c) daily gavage with 100 mg/kg masitinib, or d) combined i.p injection of 50 mg/kg gemcitabine twice a week and daily gavage with 100 mg/kg masitinib. Tumour size is measured with callipers and tumour volume is estimated using the formula: volume=(length×width2)/2. The tumour growth inhibition ratio is calculated as (100)×(median tumour volume of treated group)/(median tumour volume of control group). |
References: [1]. Dubreuil P, et al. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLoS One, 2009, 4(9), e7258. | |
Masitinib is an inhibitor of the receptor tyrosine kinase c-Kit (IC50 = 200 nM for the recombinant human enzyme).1 It is also an inhibitor of PDGFRα, PDGFRβ, and Lyn B (IC50s = 540, 800, and 510 nM, respectively). Masitinib inhibits stem cell factor-induced proliferation of Ba/F3 cells expressing wild-type KIT (IC50 = 150 nM), as well as those expressing the KIT mutants KITV559D and KITΔ27 (IC50s = 3 and 5 nM, respectively). It reduces tumor growth in a KITΔ27-expressing Ba/F3 murine model of cancer. Masitinib is also an inhibitor of the severe acute respiratory coronavirus 2 (SARS-CoV-2) main protease (Mpro; Ki = 2.6 ?M), also known as 3C-like protease (3CLpro), and inhibits replication of SARS-CoV-2 in infected A549 cells (EC50 = 3.2 ?M).2 It decreases lung and nose viral titers, as well as reduces lung inflammation and increases survival, in ACE2-humanized mice infected with SARS-CoV-2 when administered at a dose of 25 mg/kg.
1.Dubreuil, P., Letard, S., Ciufolini, M., et al.Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KITPLoS One4(9)e7258(2009) 2.Drayman, N., DeMarco, J.K., Jones, K.A., et al.Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2Science373(6557)931-936(2021)
| Cas No. | 1048007-93-7 | SDF | |
| 别名 | 甲磺酸马赛替尼; AB-1010 mesylate | ||
| Canonical SMILES | O=C(NC1=CC=C(C(NC2=NC(C3=CC=CN=C3)=CS2)=C1)C)C4=CC=C(CN5CCN(CC5)C)C=C4.CS(=O)(O)=O | ||
| 分子式 | C29H34N6O4S2 | 分子量 | 594.75 |
| 溶解度 | DMSO: ≥ 30 mg/mL (50.44 mM) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6814 mL | 8.4069 mL | 16.8138 mL |
| 5 mM | 0.3363 mL | 1.6814 mL | 3.3628 mL |
| 10 mM | 0.1681 mL | 0.8407 mL | 1.6814 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Effects of Tyrosine Kinase Inhibitor-masitinib Mesylate on Canine Mammary Tumour Cell Lines
J Vet Res 2021 Jul 24;65(3):351-359.PMID:34917849DOI:10.2478/jvetres-2021-042.
Introduction: Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action. Material and methods: The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells. Results: Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC50 of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells. Conclusion: In this study, masitinib suppressed cell proliferation concomitantly via induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells in vitro, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.
Masitinib mesylate does not enhance sensitivity to radiation in three feline injection-site sarcoma cell lines under normal growth conditions
Res Vet Sci 2014 Apr;96(2):304-7.PMID:24602916DOI:10.1016/j.rvsc.2014.02.001.
Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. Sensitivity to masitinib was previously assessed via cell growth inhibition assays with mean IC50 values of 5.5-8.6μM. Clonogenic assays were performed to determine the effect of masitinib and radiation on cell survival. Single dose radiation (0-12Gy) experiments were carried out under normal growth conditions in control ISS cells and in cells incubated with 1 or 6μM masitinib for 72h prior to irradiation. Radiation administered either alone or in combination with masitinib induced a dose-dependent reduction in clonogenic survival. Survival from the combined masitinib and radiation treatment was not significantly different from that of radiation alone. Results suggest that masitinib does not directly enhance ISS cell radiosensitivity under normal in vitro conditions, although this does not preclude the utility of further investigations to assess sensitization properties under altered conditions.
Masitinib mesylate for metastatic and non-resectable canine cutaneous mast cell tumours
Vet Comp Oncol 2015 Sep;13(3):314-21.PMID:23845124DOI:10.1111/vco.12053.
Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non-metastatic grade II and III canine mast cell tumours (MCTs). This study evaluated the use of masitinib as a frontline and rescue agent for metastatic and non-metastatic canine MCTs. Identification of toxicities and prognostic factors in these dogs was of secondary interest. Twenty-six dogs were included in this study. The overall response rate to masitinib was 50%. The median survival time for dogs that responded to masitinib was 630 days versus 137 days for dogs that did not respond (P = 0.0033). Toxicity was recorded in 61.5% of treated dogs, but the majority of adverse events were mild and self-limiting. Response to masitinib, not tumour grade, stage or location, was the most significant prognostic factor for survival in dogs with MCTs.
Clinical response of Masitinib mesylate in the treatment of canine macroscopic mast cell tumours
J Small Anim Pract 2016 Jun;57(6):283-90.PMID:27136424DOI:10.1111/jsap.12480.
Objectives: To retrospectively evaluate the clinical response and toxicity associated with Masitinib mesylate (Masivet®) treatment of macroscopic mast cell tumours in the dog. Methods: Retrospective review of medical records of 39 dogs that had undergone treatment with masitinib for macroscopic mast cell tumours. Patient signalment, tumour location, tumour grade, tumour stage, previous treatments, concurrent medications, dose of masitinib, side effects, response, time to tumour progression, survival time and cause of death were documented. Response was assessed according to RECIST criteria. Results: Clinical response was observed in 32 (82·1%) dogs receiving masitinib, with 15 dogs (38·5%) exhibiting a complete response and 17 dogs (43·6%) achieving a partial response. The median time to progression was 79 days (range: 14 to 667 days). Adverse effects were seen in 25 dogs (64·1%) with serum alanine aminotransferase elevation (n=9; 23·1%) and vomiting (n=6; 15·4%) being most common. Median survival time following initiation of masitinib was 159 days (range: 14 to 1339). Clinical significance: Masitinib appears to be a well-tolerated and effective drug against macroscopic mast cell tumours.
Safety of Masitinib mesylate in healthy cats
J Vet Intern Med 2011 Mar-Apr;25(2):297-302.PMID:21314730DOI:10.1111/j.1939-1676.2011.0687.x.
Background: Masitinib mesylate is a PO-administered tyrosine kinase inhibitor developed both for human and animal diseases with activity against both mutated and wild type forms of the c-kit receptor and platelet-derived growth factor receptors α and β, and is currently registered in Europe for the treatment of mast cell tumors in dogs. Hypothesis/objectives: The objective of this study was to determine if healthy cats can tolerate administration of masitinib without clinically relevant adverse effects. Animals: Twenty healthy research colony-specific pathogen-free cats. Methods: This study was a prospective, randomized phase 1 clinical trial. Masitinib was administered PO to 20 healthy cats. Ten cats received 50 mg masitinib every other day for 4 weeks, and 10 cats received 50 mg masitinib daily for 4 weeks. Results: Clinically relevant proteinuria was noted in 2/20 (10%) cats (both treated daily), and neutropenia was noted in 3/20 (15%) (seen in both treatment groups). An increase in serum creatinine concentration and adverse gastrointestinal effects were noted in some cats. Conclusions and clinical importance: Masitinib mesylate was tolerated in the majority of cats. Long-term administration and pharmacokinetic studies are needed to further assess the use of masitinib in cats.