Tipifarnib (IND 58359) 抑制法尼基转移酶 (FTase),IC50为 0.86 nM。Tipifarnib 具有潜在抗肿瘤活性。
生物活性 | Tipifarnib (IND 58359) binds to and inhibitsfarnesyltransferase (FTase)with anIC50of 0.86 nM. Antineoplastic activity[1]. |
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体外研究 (In Vitro) | Tipifarnib inhibits the growth of H-Ras-transformed NIH 3T3 cells with an impressive IC50value of 1.7 nM[1]. Tipifarnib is a potent inhibitor ofTrypanosoma Cruziwith the ED50of 4 nM[1]. Combining Tipifarnib with 10 nM 4-OH-ICI 47699 in the presence of E2 reduces the IC508-fold from 400 to 50 nM[2]. Tipifarnib inhibits isolated human farnesyltransferase for a lamin B peptide and for the K-RasB peptide with IC50of 0.86 nM and 7.9 nM, respectively[3]. Tipifarnib shows inhibition of cell growth or angiogenesis, and induction of apoptosis in aggressive prostate cancer (PCa)[4]. Tipifarnib shows a significant decrease in the concentration of exosomes in C4-2B cells both at 0.25 and 1 μM as well as in the PC-3 cells at 0.25 μM for 48 hours[4]. Tipifarnib (1 μM) significantly inhibits the protein concentration of Alix, nSMase2, and Rab27a in C4-2B cells[4]. Tipifarnib (0.25 μM) significantly inhibits the activation of p-ERK (downstream effector molecule of the Ras/Raf/ERK signaling pathway) but not total ERK in C4-2B and PC-3 cells but not in the normal RWPE-1 cells[4]. Tipifarnib (0-250 nM) causes a dose-dependent decrease in Alix, nSMase2, and Rab27a in both C4-2B and PC-3 cells, but not in the RWPE-1 cells, Tipifarnib has the potential to be a potent inhibitor of exosome biogenesis and/or secretion[4].
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体内研究 (In Vivo) | Combined therapy with ICI 47699 and Tipifarnib (50 mg/kg, p.o.) produces greater tumor growth inhibition when compared with either drug alone. E2 deprivation and Tipifarnib in combination results in greater growth inhibition than either E2 deprivation or Tipifarnib alone. The combination of ICI 47699 and Tipifarnib results in significantly lower Ki-67 compared with either ICI 47699 or Tipifarnib alone. Tipifarnib alone also reduces the CTI compared with control. The combination of ICI 47699 and Tipifarnib or Tipifarnib coupled with E2 withdrawal is most effective at lowering the CTI (0.8 and 0.7, respectively), which may account for the decrease in tumor volume[2].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 100 mg/mL(204.33 mM;Need ultrasonic) 配制储备液 1 mM | 2.0433 mL | 10.2166 mL | 20.4332 mL | 5 mM | 0.4087 mL | 2.0433 mL | 4.0866 mL | 10 mM | 0.2043 mL | 1.0217 mL | 2.0433 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 20%HP-β-CD/10 mM citrate pH 2.0 Solubility: 10 mg/mL (20.43 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1.43 mg/mL (2.92 mM); Clear solution
此方案可获得 ≥ 1.43 mg/mL (2.92 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 14.3 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 1.43 mg/mL (2.92 mM); Suspended solution; Need ultrasonic
此方案可获得 1.43 mg/mL (2.92 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 14.3 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 4. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 1.43 mg/mL (2.92 mM); Clear solution
此方案可获得 ≥ 1.43 mg/mL (2.92 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 14.3 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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