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Lonafarnib

现货
Catalog No.
A4379
高效且具有选择性的法尼基转移酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,700.00
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5mg
¥ 1,190.00
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10mg
¥ 1,890.00
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100mg
¥ 13,090.00
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200mg
¥ 19,390.00
Ship with 10-15 days

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Background

Lonafarnib (SCH66336, Sarasar) is an potent, selective, orally, bioavailable tricyclic nonpeptidyl nonsulfhydry inhibitor of farnesyltransferase (FTase).[1] It is a small molecular with the formula of C27H31Br2ClN4O2 and molecular weight of 638.82. Farnesylated Ras proteins was found to regulate signal transduction pathways which drive cell proliferation, growth and survival and be required for its membrane localization.[1, 2] Lonafarnib inhibits the post-translational farnesylcation of ras proteins, therefore blocking translocation of RAS to the plasma membrane.[3]

Reference

[1] Eric W, Malcolm J. M, Kim N. C, D. Scott E, et al. A multinomial Phase II study of lonafarnib (SCH 66336) in patients with refractory urothelial cancer. Urologic Oncology: Seminars and Original Investigations. 2005, 23. 143-149.

[2] Gongjie L, Stacey A. T, Cindy H. M, Yunsheng H, W. Robert B, et al. Continuous and intermittent dosing of lonafarnib potentiates the therapeutic efficacy of docetaxel on preclinical human prostate cancer models. Int. J. Cancer. 2009, 125. 2711–2720.

[3] Vasiliki A. N, Alexander J. S, Keith T. F, Hensin T, et al. Melanoma: New Insights and New Therapies. J Invest Dermatol. 2012, 132. 854–863.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt638.82
Cas No.193275-84-2
FormulaC27H31Br2ClN4O2
SynonymsSch 66336, Sch66336, Sch-66336
Solubility≥31.95 mg/mL in DMSO, ≥96.4 mg/mL in EtOH with ultrasonic, <2.5 mg/mL in H2O
Chemical Name4-[2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[1,2]cyclohepta[2,4-b]pyridin-11-yl]piperidin-1-yl]-2-oxoethyl]piperidine-1-carboxamide
SDFDownload SDF
Canonical SMILESC1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(C=C(C=C4CCC5=CC(=CN=C35)Br)Cl)Br)C(=O)N
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

UMSCC10B、UMSCC14B、UMSCC17B、UMSCC22B、UMSCC35和UMSCC38细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0.1 ~ 8 μM;24小时

实验结果

在人类头颈部鳞状细胞癌细胞(HNSCCs)中,SCH66336 (0.1 ~ 8 μM) 呈剂量和时间依赖性地抑制细胞生长并诱导细胞凋亡。

动物实验 [2]:

动物模型

携带XEN08肿瘤的NOD/SCID小鼠

给药剂量

50 mg/kg;口服给药;每日2次,持续20天

实验结果

在携带XEN08肿瘤的NOD/SCID小鼠中,SCH66336(50 mg/kg,口服给药,每日2次)显著抑制肿瘤生长,其平均生长抑制为63.8 ± 5.0%。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Chun KH, Lee HY, Hassan K, Khuri F, Hong WK, Lotan R. Implication of protein kinase B/Akt and Bcl-2/Bcl-XL suppression by the farnesyl transferase inhibitor SCH66336 in apoptosis induction in squamous carcinoma cells. Cancer Res. 2003 Aug 15;63(16):4796-800.

[2]. Feldkamp MM, Lau N, Roncari L, Guha A. Isotype-specific Ras.GTP-levels predict the efficacy of farnesyl transferase inhibitors against human astrocytomas regardless of Ras mutational status. Cancer Res. 2001 Jun 1;61(11):4425-31.

生物活性

描述 Lonafarnib是一种法尼基转移酶(FT)的抑制剂,作用于H-Ras、N-Ras、K-Ras和Rheb的IC50值分别为1.9、2.8、5.2和10-100 nM。
靶点 FT FT FT FT    
IC50 1.9 nM (H-Ras) 2.8 nM (N-Ras) 5.2 nM (K-Ras) 10-100 nM (Rheb)    

质量控制