Tipifarnib (Zarnestra) (Synonyms: R 115777)

Cell lines

Human leukemia cell line THP-1

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

100 ng/ml LPS plus 2 μM tipifarnib. 6 time points (0, 10, 20, 30, 40 and 50h)

Applications

Tipifarnib showed significant inhibition of the cytokine/ MMP-9 production as early as 20 h for MCP-1 and IL-6 and 30 h for IL-1β and MMP-9. Tipifarnib showed no significant inhibition of IL-8 production.

Animal models

Female BALB/c mice (6–7 weeks old)

Dosage form

Tipifarnib was dissolved in 20% cyclodextran, and 50 mg/kg was orally administered to mice at 24, 17, and 1 h before intraperitoneal injection of 20 μg of LPS per mouse, 1 mg/kg.

Applications

After treatment of 2h, tipifarnib significantly inhibited LPS-induced TNF-α production and inhibited 50% of MIP-1α and MCP-1 production. After 3h, tipifarnib inhibited about 50% of IL-6 production and almost complete inhibition of IL-1β production. IL12-p40 and -p70 induction by LPS was also inhibited by tipifarnib at 3 h, whereas IL-10 was not significantly changed at both time points. No effects of tipifarnib on LPS-induced KC were observed, consistent with in vitro results for IL-8.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Xue X, Lai K T A, Huang J F, et al. Anti-inflammatory activity in vitro and in vivo of the protein farnesyltransferase inhibitor tipifarnib. Journal of Pharmacology and Experimental Therapeutics, 2006, 317(1): 53-60.