Tipifarnib 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。
Tipifarnib(R115777)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。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。
|细胞系||MCF-7 cells line|
|方法||Cell Growth Assays.
Steroid-depleted cells were seeded into 12-well plates at a density of ∼1 × 104 cells per well or into 96-well plates at a density of 4,000 cells per well, in dextran-coated charcoal medium. After 24 h, monolayers were treated with E2 plus inhibitors either alone or in combination. The 12-well plates were treated for 6 days with daily changes. Cell number was then determined using a Z1 Coulter counter (Beckman Coulter). The 96-well plates were treated with a single dose and left for 96 h at which time cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as described previously (15). The interaction between R115777 and 4-OH-tamoxifen was analyzed by the median effect plot method described by Chou and Talalay (16). Calculation of the combination index took into account a nonfixed drug ratio and was based on the assumption that the action of the two drugs was mutually nonexclusive for the strict detection of synergism. A combination index < 1 indicates synergism, combination index = 1 indicates additivity, and a combination index > 1 indicates antagonism. Experiments were repeated thrice.
|动物模型||MCF-7 xenografts in Female ovariectomized Ncr foxhead nude mice|
|配制||20% w/v β-cyclodextrin (pH 2.5)|
|剂量||50 mg/kg twice daily for 5 consecutive days followed by a 2-day rest period, for a total of 19 days|
|动物 A (mg/kg) = 动物 B (mg/kg) ×||动物 B的Km系数|
例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。
|溶解性（25°C）||DMSO 14 mg/mL|
固体粉末： -20°C 冷藏长期储存
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||2.0434 mL||10.2168 mL||20.4336 mL|
|5 mM||0.4087 mL||2.0434 mL||4.0867 mL|
|10 mM||0.2043 mL||1.0217 mL||2.0434 mL|
Cancer Cell Int. 2019 Jun 11;19:159.
A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older.
Harousseau JL, et al. Blood. 2009 Aug 6;114(6):1166-73. PMID: 19470696.
Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features.
Karp JE, et al. Clin Cancer Res. 2008 May 15;14(10):3077-82. PMID: 18483374.
The farnesyltransferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo.
Martin LA, et al. Mol Cancer Ther. 2007 Sep;6(9):2458-67. PMID: 17876043.
Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma.
Alsina M, et al. Blood. 2004 May 1;103(9):3271-7. PMID: 14726402.
Adenosine Dialdehyde (ADOX)是一种腺苷类似物，同时也是S-adenosylmethionine-dependent methyltransferase抑制剂，IC50为40 nM。
Hecogenin is a potent and highly selective inhibitor of UGT1A4 with an IC50 value of 1.5 μM.
Tunicamycin is a mixture of homologous nucleoside antibiotics that inhibits the UDP-HexNAc: polyprenol-P HexNAc-1-P family of enzymes.