Tipifarnib (IND 58359) binds to and inhibits farnesyltransferase (FTase) with an IC50 of 0.86 nM. Antineoplastic activity.
体外研究
Tipifarnib inhibits the growth of H-Ras-transformed NIH 3T3 cells with an impressive IC50 value of 1.7 nM .
Tipifarnib is a potent inhibitor of Trypanosoma Cruzi with the ED50 of 4 nM.
Combining Tipifarnib with 10 nM 4-OH-ICI 47699 in the presence of E2 reduces the IC50 8-fold from 400 to 50 nM.
Tipifarnib inhibits isolated human farnesyltransferase for a lamin B peptide and for the K-RasB peptide with IC50 of 0.86 nM and 7.9 nM, respectively.
Tipifarnib shows inhibition of cell growth or angiogenesis, and induction of apoptosis in aggressive prostate cancer (PCa).
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.
Tipifarnib (1 μM) significantly inhibits the protein concentration of Alix, nSMase2, and Rab27a in C4-2B cells.
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.
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.
体内研究
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.
分子式
C27H22Cl2N4O
分子量
489.40
CAS号
192185-72-1
中文名称
替吡法尼
运输条件
Room temperature in continental US; may vary elsewhere.