Lonafarnib
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Lonafarnib（SCH66336、Sarasar）是不含肽键和巯基的三环化合物，是一种有效的、选择性的和具有生物利用度的口服法尼基转移酶（FTase）抑制剂。[1]该小分子化合物的分子式为C27H31Br2ClN4O2，分子量为638.82。法尼基化的Ras蛋白对驱动细胞增殖、生长和存活的信号转导通路具有调控作用，且对其膜定位也是不可或缺的。[1, 2]Lonafarnib可抑制ras蛋白翻译后的法尼基化反应，从而阻断RAS向质膜的易位。[3]
参考文献：
[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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 638.82 |
| Cas No. | 193275-84-2 |
| Formula | C27H31Br2ClN4O2 |
| Synonyms | Sch 66336, Sch66336, Sch-66336 |
| Solubility | ≥31.95 mg/mL in DMSO; insoluble in H2O; ≥96.4 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[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 |
| SDF | Download SDF |
| Canonical SMILES | C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(C=C(C=C4CCC5=CC(=CN=C35)Br)Cl)Br)C(=O)N |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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. |
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| 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) | ||
质量控制和MSDS
- 批次:
化学结构
