Tipifarnib (R115777)

For research use only. Not for use in humans.

目录号:S1453 别名: IND 58359 中文名称:替吡法尼

Tipifarnib (R115777) Chemical Structure

CAS No. 192185-72-1

Tipifarnib (R115777, IND 58359) 是一种有效的,特异性farnesyltransferase (FTase)抑制剂,作用于H-ras或N-ras突变细胞,具有最显著的抗增殖作用效果。Phase 3。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 5077.49 现货
RMB 3922.04 现货
RMB 8035.96 现货
RMB 16298.1 现货
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客户使用Selleck生产的Tipifarnib (R115777)发表文献30篇:

产品安全说明书

FTase抑制剂选择性比较

生物活性

产品描述 Tipifarnib (R115777, IND 58359) 是一种有效的,特异性farnesyltransferase (FTase)抑制剂,作用于H-ras或N-ras突变细胞,具有最显著的抗增殖作用效果。Phase 3。
特性 A potent and selective farnesyl protein transferase inhibitor with significant antitumor effects.
靶点
FTase [1]
()
0.6 nM
体外研究

与DMSO处理的LGL T细胞相比,用5 μM Tipifarnib处理72小时,凋亡细胞百分率明显高很多。使用健康捐赠者提供的T细胞,Tipifarnib按剂量依赖性降低IFNγ阳性细胞百分率。在沉淀物中,与DMSO相比,Tipifarnib降低激活型Ras的数量。[2]在体外,Tipifarnib浓度低于10 nM时,选择性在克隆性骨髓增生异常综合征(MDS)造血作用中产生毒性,当白细胞存在时这种作用更显著。用Tipifarnib处理72小时,正常MDS前体表达出等量的DiOC3和膜联蛋白V。[3] Tipifarnib和10 nM 4-OH-tamoxifen联用,在有E2存在时,使IC50值降低8倍,从400 nM降低到50 nM。[4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 cells NEDtUJlHfW6ldHnvckBie3OjeR?= M3fYSGlvcGmkaYTpc44hd2ZicnH0JJJm[2:vYnnuZY51KFCIVDDlfJBz\XO|ZXSgbY4hcW6|ZXP0JHNnQSClZXzsd{BjgSC|Y3nueIltdGG2aX;uJJBzd3irbXn0fUBie3OjeTygTWM2OD1yLkegcm0> MlXpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB2Mkm1NVEoRjJyNEK5OVEyRC:jPh?=
NIH3T3 cells M1;R[mZ2dmO2aX;uJIF{e2G7 NHX1XJRKdmirYnn0bY9vKG:oIGLhd{Bxem:lZYPzbY5oKGmwIFitdoF{KHS{YX7z[o9zdWWmIF7JTFNVOyClZXzsd{BqdiCycnXz[Y5k\SCxZjDUbZBq\mG{bnniMEBGSzVyPUGuOkBvVQ>? MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTlzMUK4NUc,OTV7MUGyPFE9N2F-
NIH 3T3 NVnveo57TnWwY4Tpc44h[XO|YYm= MmDhSYZn\WO2aY\lJINwdmOnboTyZZRqd25iYXfhbY5{fCCKYT3SRXMheHKxY3Xzd4lv\yCrbjDOTWg{XDNicnHzMZRz[W6|Zn;ycYVlKGOnbHzzMEBGSzVyIE2gNE4xODJizszNMi=> MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yOjZ3N{K4OEc,OTJ4NUeyPFQ9N2F-
NIH 3T3 NEXs[VJHfW6ldHnvckBie3OjeR?= MXXJcohq[mm2aX;uJI9nKFR{NF[xTE1z[XNvdILhcpNnd3KvYYTpc44hcW5iTlnIJFNVOyClZXzsd{whUUN3MDC9JFAvODBzNzFOwG0v MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yOjZ7OUe1NUc,OTJ4OUm3OVE9N2F-
NIH 3T3 M37ze2Z2dmO2aX;uJIF{e2G7 Ml7qTY5pcWKrdHnvckBw\iCUYYOg[oFzdmW|eXzheIlwdiCrbjDIMXJieyC2cnHud4Zwem2nZDDOTWg{XDNiY3XscJMtKEWFNUCgQUAxNjByMU[g{txONg>? MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTR3NEKyPEc,OTV2NUSyNlg9N2F-
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HAL-01 NUfh[m9JT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MkL3TY5pcWKrdHnvckBw\iCqdX3hckBJSUxvMEGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3MDC9JFYvPzN7OUGg{txONg>? Mo\PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlg6OjJ6Lze+V2FPT0WUPD;hQi=>
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Caspase-12 / PARP1; 

PubMed: 21378206     


Western blot analysis of protein extracts from U937 cells incubated in normal media (Control) or media containing tipifarnib at the indicated concentrations. Extracts were probed using antibodies directed against cleaved caspase-12, PARP1 (full-length and cleaved), and β-actin, with the latter used as a lane loading reference. 

Rheb / p-mTOR / mTOR / p-P70S6K / P70 S6K / p-S6 / S6 ; 

PubMed: 23996484     


After U937 cells were treated for 24 h with the indicated tipifarnib concentration, whole cell lysates were subjected to immunoblotting with antibodies that recognize the indicated antigens. GAPDH served as a loading control. In this and subsequent figures, gray arrow indicates farnesylated antigen and black arrow indicates unfarnesylated antigen. 

Bcl-2 / Bcl-xl / Mcl-1 / Bax / Bak / Puma / Noxa / Bim / Lamin B; 

PubMed: 23996484     


After U937 cells were treated for 6 days with the indicated tipifarnib concentration, whole cell lysates were subjected to immunoblotting with antibodies that recognize the indicated polypeptides.

HDJ-2 / N-Ras / FKBP51 / p-AKT / AKT; 

PubMed: 23996484     


Whole cell lysates prepared from parental U937 cells treated for 48 h with diluent or 800 nM tipifarnib (lanes 2 and 3, respectively) or from tipifarnib-resistant cells growing in 800 nM tipifarnib (lane 1) were subjected to SDS-PAGE followed by immunoblotting with antibodies that recognize the indicated antigen.

p-c-Raf / c-Raf / p-MEK / MEK / p-ERK / ERK; 

PubMed: 21673341     


After Jurkat cells were treated for 72 hours with the indicated tipifarnib concentration in the presence of 5μM Q-VD-OPh, whole cell lysates were subjected to immunoblotting with antibodies that recognize the indicate polypeptides. Ribosomal protein S6 and Hsp90 served as loading controls. 

21378206 23996484 21673341
Growth inhibition assay
Cell viability; 

PubMed: 26630652     


NCI-H929, INA6, MM.1S, and RPMI-8226 MM cell lines were cultured with tipifarnib (0–20 μM), dabrafenib (0–20 μM), or AZD6244 (0–20 μM) for 72 h. In each case, cell viability was assessed with the MTT assay of triplicate cultures and expressed as the percentage of the untreated control. Data are the mean ± SD.

26630652
体内研究 与单独使用E2处理的肿瘤相比,E2联用R115777处理的肿瘤中Ki-67降低。与分别单独使用Tamoxifen 或 R115777相比,Tamoxifen和R115777联用导致Ki-67明显降。然而,在不同组别中凋亡没有明显区别。R115777单独处理也降低CTI。Tamoxifen和R115777或R115777及E2联用作用于降低CTI更有效, 可以导致肿瘤体积降低。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

细胞实验:[4]
- 合并
  • Cell lines: 选定的MACS CD34+细胞
  • Concentrations: 2.5, 10, 25和50 nM
  • Incubation Time: 48小时
  • Method: 选定的MACS CD34+细胞接种在含1%牛血清蛋白的甲基纤维素培养基上, 3 U/ml重组人类(rh)促红细胞生成素, 10-4 M 2-巯基乙醇, 2 mM L-谷氨酸,及如下细胞因子: 50 ng/ml rh干细胞因子, 20 ng/ml rh GM-CSF, 20 ng/ml rh IL-3, 20 ng/ml rh IL-6和20 ng/ml rh G-CSF。第一天,对照组加入DMSO,实验组分别加浓度为2.5, 10, 25 和50 nM的Tipifarnib。在含5% CO2的湿润孵卵器中37oC环境下温育14天后,获得群落数。
    (Only for Reference)
动物实验:[4]
- 合并
  • Animal Models: 切除卵巢的雌性Ncr foxhead裸鼠
  • Dosages: 50 mg/kg
  • Administration: 口服饲喂
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 14 mg/mL (28.6 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
15% Captisol+citrate vehicle
5 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 489.4
化学式

C27H22Cl2N4O

CAS号 192185-72-1
储存条件 粉状
溶于溶剂
别名 IND 58359

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04997902 Recruiting Drug: Tipifarnib|Drug: Alpelisib HNSCC Kura Oncology Inc. December 7 2021 Phase 1|Phase 2
NCT04865159 Recruiting Drug: Tipifarnib Advanced Solid Tumor Kura Oncology Inc. May 6 2021 Phase 1
NCT04284774 Recruiting Drug: Tipifarnib Recurrent Adrenal Gland Pheochromocytoma|Recurrent Ectomesenchymoma|Recurrent Ependymoma|Recurrent Ewing Sarcoma|Recurrent Hepatoblastoma|Recurrent Kidney Wilms Tumor|Recurrent Langerhans Cell Histiocytosis|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Glioma|Recurrent Medulloblastoma|Recurrent Melanoma|Recurrent Neuroblastoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Osteosarcoma|Recurrent Peripheral Primitive Neuroectodermal Tumor|Recurrent Rhabdoid Tumor|Recurrent Rhabdoid Tumor of the Kidney|Recurrent Rhabdomyosarcoma|Recurrent Soft Tissue Sarcoma|Recurrent Thyroid Gland Carcinoma|Recurrent WHO Grade II Glioma|Refractory Adrenal Gland Pheochromocytoma|Refractory Ependymoma|Refractory Ewing Sarcoma|Refractory Hepatoblastoma|Refractory Langerhans Cell Histiocytosis|Refractory Malignant Germ Cell Tumor|Refractory Malignant Glioma|Refractory Medulloblastoma|Refractory Melanoma|Refractory Neuroblastoma|Refractory Non-Hodgkin Lymphoma|Refractory Osteosarcoma|Refractory Peripheral Primitive Neuroectodermal Tumor|Refractory Rhabdoid Tumor|Refractory Rhabdoid Tumor of the Kidney|Refractory Rhabdomyosarcoma|Refractory Soft Tissue Sarcoma|Refractory Thyroid Gland Carcinoma|Refractory WHO Grade II Glioma National Cancer Institute (NCI) July 13 2020 Phase 2
NCT03719690 Recruiting Drug: Tipifarnib|Device: HRAS Detection Assay HRAS Gene Mutation|HNSCC Kura Oncology Inc. November 5 2018 Phase 2
NCT03496766 Recruiting Drug: Tipifarnib Non Small Cell Lung Cancer Spanish Lung Cancer Group May 7 2018 Phase 2
NCT02807272 Completed Drug: Tipifarnib Leukemia Myelomonocytic Chronic Kura Oncology Inc. October 2016 Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID