| 名稱 | Masitinib |
| 描述 | Masitinib (AB1010) is a tyrosine-kinase inhibitor used in the treatment of mast cell tumors in animals, specifically dogs. Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. In the USA it is distributed under the name Kinavet and has been available for veterinaries since 2011. |
| 細(xì)胞實(shí)驗(yàn) | 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. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro enzyme-linked immunoassay with recombinant protein kinases: 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 5?M urea 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. |
| 體外活性 | 與安慰劑相比,Masitinib（12.5 mg/kg/d PO）可增加狗的總體TTP（腫瘤進(jìn)展時(shí)間）.在表達(dá)Δ27的Ba/F3 移植瘤模型中,30 mg/kg Masitinib抑制腫瘤生長(zhǎng)和提高平均存活時(shí)間,沒(méi)有心臟毒性或遺傳毒性.Masitinib和吉西他濱聯(lián)用表現(xiàn)出對(duì)抗吉西他濱的細(xì)胞系Mia Paca2和Panc1增殖的協(xié)同抑制作用. |
| 體內(nèi)活性 | Masitinib抑制表達(dá)人類野生型KIT的Ba/F3的細(xì)胞中干細(xì)胞因子誘導(dǎo)的細(xì)胞增殖,IC50為150 nM,而抑制IL-3刺激的增殖時(shí),IC50值約>10 μM。Masitinib在表達(dá)PDGFR-α的Ba/F3細(xì)胞中,抑制PDGF-BB刺激的增殖和 PDGFR-α 酪氨酸磷酸化作用,IC50為300 nM。Masitinib濃度≤500 nM時(shí)為ATP競(jìng)爭(zhēng)性抑制劑。Masitinib也有效抑制重組PDGFR和胞內(nèi)激酶Lyn及FGFR 3。 然而,Masitinib對(duì)ABL和c-Fms抑制效果很弱。在哺乳動(dòng)物細(xì)胞系和BMMC中,馬西替尼還能抑制SCF刺激的人Kit酪氨酸磷酸化。Masitinib抑制Ba/F3細(xì)胞中KIT獲得的功能突變,包括V559D突變和Δ27鼠突變,IC50分別為3和5 nM。在兩種新型ISS細(xì)胞系中,Masitinib抑制細(xì)胞生長(zhǎng)和PDGFR磷酸化,這表明Masitinib顯示針對(duì)原發(fā)性和轉(zhuǎn)移性ISS細(xì)胞系的活性,并可能有助于ISS的臨床管理。Masitinib對(duì)脫顆粒,細(xì)胞因子產(chǎn)生和骨髓肥大細(xì)胞遷移的抑制效果比imatinib強(qiáng)很多。Masitinib抑制肥大細(xì)胞瘤細(xì)胞系包括 HMC-1α155和FMA3的細(xì)胞增殖,IC50分別為10和30 nM。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 60 mg/mL (120.33 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 4 mg/mL (8.02 mM)
|
| 關(guān)鍵字 | PTK2 | SCFR | PDGFR | Src | inhibit | c-Kit | Apoptosis | CD117 | Focal adhesion kinase | PTK2 protein tyrosine kinase 2 | AB-1010 | FAK | FGFR | Inhibitor | Platelet-derived growth factor receptor | Fibroblast growth factor receptor | Masitinib | AB 1010 |
| 相關(guān)產(chǎn)品 | Metronidazole | Ferulic Acid | 5-Fluorouracil | Stavudine | Tributyrin | Dextran sulfate sodium salt (MW 4500-5500) | Myricetin | Sorafenib | L-Ascorbic acid | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌上市藥物庫(kù) | 抗癌活性化合物庫(kù) | 激酶抑制劑庫(kù) | 膜蛋白靶向化合物庫(kù) | 神經(jīng)退行性疾病化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |