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Sunitinib malate

现货
Catalog No.
A8255
VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
100mg
¥ 500.00
现货
500mg
¥ 1,000.00
现货
1g
¥ 1,500.00
现货
2g
¥ 2,000.00
现货

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Background

Sunitinib malate, also called sunitinib, is a novel, oral, multi-targeted , small molecule oxindole tyrosine kinase inhibitor which inhibits multiple receptor tyrosine kinases including platelet-derived growth factor receptor ( and (, vascular endothelial growth factor receptor 1, 2 and 3, c-KIT, FLT3 kinase, colony-stimulating factor 1 receptor and RET kinase [2][3] [4]. The IC50 of sunitinib is approximately 10-20 ng/ml to NB cell lines, which is within the clinically relevant human trough serum concentration (50-100 ng/ml) [1].

Receptor tyrosine kinases activated a number of different intracellular signaling pathways [5].

In neuroblastoma (NB) cell lines, SKN-BE (2), NUB-7, SH-SY5Y and LAN-5, sunitinib significantly inhibited cell proliferation after a treatment for 48 hours, in a concentration-dependent manner [1].

Treatment with 20, 30 or 40 mg/kg of sunitinib made NOD/SCID mice inoculated with xenograft tumor cells show significant reduction (P

References:
[1].  Libo Zhang, Kristen M. Smith, Amy Lee Chong, et al. In Vivo Antitumor and Antimetastatic Activity of Sunitinib in Preclinical Neuroblastoma Mouse Model. Neoplasia, 2009, 11: 426-435.
[2].  Hassane Izzedine, Irina Buhaescu, Olivier Rixe, et al. Sunitinib malate. Cancer Chemother Pharmacol, 2007, 60: 357-364.
[3].  M. L. Telli, R. M. Witteles, G. A. Fisher, et al. Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Annals of Oncology, 2008, 19: 1613–1618.
[4].  Edwin P. Rock, Vicki Goodman, Janet X. Jiang, et al. Food and Drug Administration Drug Approval Summary: Sunitinib Malate for the Treatment of Gastrointestinal Stromal Tumor and Advanced Renal Cell Carcinoma. The Oncologist, 2007, 12: 107-113.
[5].  C. J. Marshall. Specificity of Receptor Tyrosine Kinase Signaling: Transient versus Sustained Extracellular Signal-Regulated Kinase Activation. Cel, 1995, 80: 179-185.

文献引用

1. Wu F, Wu D, et al. "Generation of hepato-biliary organoids from human induced pluripotent stem cells." J Hepatol. 2019 Jan 7. pii: S0168-8278(19)30002-9. PMID:30630011
2. Lin M, Chen B. "Advances in the drug therapies of acute myeloid leukemia (except acute wpromyelocytic leukemia)." Drug Des Devel Ther. 2018 Apr 30;12:1009-1017. PMID:29750014

Chemical Properties

Physical AppearanceA solid
StorageStore at 4°C
M.Wt532.56
Cas No.341031-54-7
FormulaC22H27FN4O2.C4H6O5
SynonymsSU 11248,SU11248,SU-11248,Sunitinib
Solubility≥26.65mg/mL in DMSO, <2.45 mg/mL in EtOH, ≥4.6 mg/mL in H2O with ultrasonic
Chemical NameN-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide;(2S)-2-hydroxybutanedioic acid
SDFDownload SDF
Canonical SMILESCCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C.C(C(C(=O)O)O)C(=O)O
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]:

细胞系

NIH-3T3细胞,HUVECs

溶解方法

该化合物在DMSO中的溶解度大于10 mM.。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。

应用

在血清饥饿的表达VEGFR2或PDGFRβ的NIH-3T3细胞中,Sunitinib抑制VEGF依赖性VEGFR2磷酸化和PDGF依赖性PDGFRβ磷酸化。Sunitinib抑制VEGF诱导的血清饥饿HUVEC的增殖,IC50为40 nM,抑制PDGFβ或PDGFRα过表达的NIH-3T3细胞中PDGF诱导的增殖,IC50分别为39 nM和69 nM。

动物实验 [1]:

动物模型

携带HT-29、A431、Colo205、H-460、SF763T、C6、A375或MDA-MB-435细胞的肿瘤异种移植小鼠模型

给药剂量

口服给药,20-80 mg/kg/day,每日一次

应用

Sunitinib (20-80 mg/kg/day)对各种肿瘤异种移植模型表现出广泛和有效的剂量依赖性抗肿瘤活性,包括HT-29、A431、Colo205、H-460、SF763T、C6、A375或MDA-MB-435。Sunitinib (80 mg/kg/day) 处理21天导致8只小鼠中的6只完全的肿瘤消退,在治疗结束后的110天观察期间没有肿瘤再生长现象。Sunitinib显著降低肿瘤MVD,在SF763T胶质瘤肿瘤中减少约40%。SU11248完全抑制了表达荧光素酶的PC-3M异种移植物额外的肿瘤生长,尽管肿瘤大小没有减少。

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]. Mendel D B, Laird A D, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors[J]. Clinical Cancer Research, 2003, 9(1): 327-337.

生物活性

描述 Sunitinib malate是VEGFR2和PDGFRβ的RTK多靶点抑制剂,IC50值为80 nM 和2 nM。
靶点 VEGFR2 (Flk-1) PDGFRβ        
IC50 80 nM 2 nM        

质量控制

化学结构

Sunitinib malate

相关生物数据

Sunitinib malate

相关生物数据

Sunitinib malate

相关生物数据

Sunitinib malate