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Purity: ≥98%
Tipifarnib (R-115777; LX-81; R115777; NSC-702818; D03720; Zarnestra), non-peptidomimetic quinolinone analog, is a potent and selective farnesyltransferase (FTase) inhibitor with potential antineoplastic activity. Tipifarnib inhibits farnesyltransferase with an IC50 of 0.6 nM. It exhibits excellent anti-proliferative activity in vitro against H-ras or N-ras mutant cells. Tipifarnib was studied in patients with myeloid leukemia (AML). It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive.
| ln Vitro |
Tipifarnib, having an ED50 of 4 nM, is a strong inhibitor of Trypanosoma Cruzi. With an IC50 of 0.86 nM for lamin B peptide and 7.9 nM for K-RasB peptide, respectively, tipifarnib inhibits the isolated human farnesyl transferases of these two biomolecules [2]. In cases of aggressive prostate cancer (PCa), tipifarnib reduces angiogenesis and cell proliferation while inducing apoptosis [3]. The quantity of exosomes in C4-2B and PC-3 cells was significantly reduced by tipifarnib (0.25 μM, 1 μM; 48 h) [3]. Alix, nSMase2, and Rab27a protein quantities in C4-2B cells are dramatically inhibited by tipifarnib (1 μM) [3]. When applied to C4-2B and PC-3 cells, tipifarnib (0.25 μM) strongly suppresses the activation of p-ERK, a downstream effector molecule of the Ras/Raf/ERK signaling pathway, but does not reduce total ERK [3]. A 30 minute exposure to tipifarnib (1.25-5 μM) causes endoplasmic reticulum stress in U937 cells, which in turn causes an imbalance in intracellular calcium homeostasis [4].
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| ln Vivo |
In mice, tipifarnib (10 mg/kg; intraperitoneal injection; single dose) inhibits the mortality caused by GalN/LPS by upregulating the liver anti-apoptotic protein Bcl-xL [5].
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| Animal Protocol |
Animal/Disease Models: GalN/LPS challenge mouse[5]
Doses: 10 mg/kg; while chanllenge with GalN (400 mg/kg; IP) and LPS (32 g/kg) Route of Administration: IP; 60 min before challenge Experimental Results: Protected primary hepatocytes from GalN/tumor necrosis factor-induced cell death. Inhibited caspase 3 activation and upregulating antiapoptotic proteins. |
| References |
[1]. Devendra S Puntambekar, et al. Inhibition of farnesyltransferase: a rational approach to treat cancer? J Enzyme Inhib Med Chem. 2007 Apr;22(2):127-40.
[2]. End DW, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 2001 Jan 1;61(1):131-7 [3]. Amrita Datta, et al. High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. Sci Rep. 2018 May 25;8(1):8161. |
| Molecular Formula |
C27H22CL2N4O
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| Molecular Weight |
489.4
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| CAS # |
192185-72-1
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| Related CAS # |
Tipifarnib (S enantiomer);192185-71-0
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| SMILES |
O=C1N(C2=C(C(C3=CC=CC(Cl)=C3)=C1)C=C(C=C2)[C@@](N)(C4=CN=CN4C)C5=CC=C(C=C5)Cl)C
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| Synonyms |
R115777; R 115777; R-115777; LX81; NSC702818; D03720; trade name Zarnestra
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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