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Masitinib (AB1010)

现货
Catalog No.
A2942
酪氨酸激酶抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 500.00
现货
25mg
¥ 1,000.00
现货
100mg
¥ 3,000.00
现货

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Background

The stem cell factor receptor (KIT) is a therapeutic target for the cancer, mastocytosis, and inflammatory diseases treatment. Masitinib (AB1010) is a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT.
In vitro: Masitinib potently inhibited the intracellular kinase Lyn and recombinant PDGFR as well as fibroblast growth factor receptor 3. Moreover, masitinib showed weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. These findings suggest that Masitinib (AB1010) will exhibit a better safety profile than other tyrosine kinase inhibitors; in fact, masitinib-induced genotoxicity or cardiotoxicity has not been observed in animal so far [1].
In vivo: In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. We found that tumour growth was blocked following 5 days of treatment with masitinib. After withdrawal of masitinib treatment after day 5, tumour growth was once again evident [1].
Clinical trial: A Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). Thirty patients were enrolled with a median follow-up of 34 months. Masitinib appears to be effective as a first-line treatment of advanced GIST with comparable results to imatinib in terms of safety and response. PFS and OS results data show promise that masitinib may provide sustainable benefits [2].
Reference:
[1] Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W, Voisset E, Arock M, Auclair C, Leventhal PS, Mansfield CD, Moussy A, Hermine O. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One. 2009;4(9):e7258.
[2] Sylvie Bonvalot , Alain Moussy , Jean-Pierre Kinet , et al. Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). European Journal of Cancer. 2010(46): 1344-1351

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt498.64
Cas No.790299-79-5
FormulaC28H30N6OS
Solubility≥24.95mg/mL in DMSO
Chemical Name4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide
SDFDownload SDF
Canonical SMILESCC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC(=CS4)C5=CN=CC=C5
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1,2]:

细胞系

Ba/F3细胞,HMC-1α155和FMA3细胞,骨髓细胞

溶解方法

该化合物在DMSO中的溶解度大于25 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

37°C

应用

Masitinib抑制人肥大细胞脱颗粒、细胞因子产生和骨髓细胞迁移。在Ba/F3细胞中,masitinib以剂量依赖性方式抑制与GIST(外显子11)相关的V559D突变体诱导的细胞增殖,IC50为3.0 ± 0.1 nM。Masitinib以剂量依赖性方式抑制Ba/F3细胞的Δ27 KIT依赖性增殖,IC50为5.0 ± 0.3nM。在携带近端结构域KIT突变的HMC-1α155和FMA3细胞中,IC50值分别为约10±1 nM和30 ± 1.5 nM。Masitinib抑制SCF刺激的细胞增殖和KIT的酪氨酸磷酸化,IC50为200 ± 50 nM。在原发性和转移性ISS细胞系中,Masitinib抑制细胞生长和PDGFR磷酸化。

动物实验 [1,3]:

动物模型

Ba/F3 Δ27肿瘤模型

给药剂量

口服,30或45 mg/kg,每天两次,持续10天

应用

在小鼠中,Masitinib治疗以剂量依赖性方式抑制肿瘤生长。与安慰剂组相比,30或45 mg/kg的Masitinib治疗11天后的肿瘤生长显著降低,在masitinib治疗的小鼠中,平均肿瘤体积分数增加了355%和154%。口服给予100 mg/kg剂量masitinib的小鼠具有大的表达Δ27 KIT的肿瘤。与给予安慰剂狗相比,Masitinib(12.5 mg/kg/d, p.o.)增加了总体TTP(时间-肿瘤进展)。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Dubreuil P, Letard S, Ciufolini M, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT[J]. PloS one, 2009, 4(9): e7258.

[2]. Lawrence J, Saba C, Gogal R, et al. Masitinib demonstrates anti‐proliferative and pro‐apoptotic activity in primary and metastatic feline injection‐site sarcoma cells[J]. Veterinary and comparative oncology, 2012, 10(2): 143-154.

[3]. Hahn K A, Oglivie G, Rusk T, et al. Masitinib is safe and effective for the treatment of canine mast cell tumors[J]. Journal of Veterinary Internal Medicine, 2008, 22(6): 1301-1309.

生物活性

Description 马赛替尼(masitinib)是一种强效的、选择性的酪氨酸激酶抑制剂,对KIT、PDGFRα及PDGFRβ的IC50值分别为200 nM、540 nM及800 nM。
靶点 KIT PDGFRα PDGFRβ      
IC50 200 nM 540 nM 800 nM      

质量控制