• Tipifarnib, also known as R115777, is a potent, selective, non-peptide inhibitor of farnesyl protein transferase that has significant antitumor effects in vivo. It competitively inhibited the farnesylation of lamin B (IC50 = 0.86 nM) and K-RasB (IC50 = 7.9 nM) peptide substrates and inhibited the cell growth of ~75% of a panel of 53 human tumor cell lines tested. Tipifarnib produced a prominent antiangiogenic response in LoVo human colon tumors, an antiproliferative response in CAPAN-2 human pancreatic tumors, and apoptosis in C32 human melanoma. End, D.W., et al. "Characterization of the Antitumor Effects of the Selective Farnesyl Protein Transferase Inhibitor R115777 in Vivo and in Vitro." Cancer Res. 61: 131-137 (2001).
• Tipifarnib significantly reduced daunorubicin efflux in CCRF-CEM cells (IC50 < 0.5 µM). It also inhibited cellular proliferation and induced apoptosis synergistically with daunorubicin. Tipifarnib has both P-glycoprotein inhibitory activity and farnesyl transferase inhibitory activity. Medeiros, B.C., et al. "The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines." Leukemia 21: 739-746 (2007).
• Tipifarnib significantly decreased (>85%) the proliferative index and increased apoptosis by about 5-fold in all mammary cancers with HaRas mutations, whereas variable responses were observed in cancers without HaRas mutations. Lubet, R.A., et al. "Effects of the farnesyl transferase inhibitor R115777 (Zarnestra) on mammary carcinogenesis: prevention, therapy, and role of HaRas mutations." Mol. Cancer Ther. 5: 1073-1078 (2006).
• Treatment with tipifarnib inhibited cell growth in vitro and tumor growth in vivo, caused increased apoptosis and decreased proliferation, and reduced the cell turnover index. Wärnberg, F., et al. "Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo." Breast Cancer Res. 8: R21-R30 (2006).
• Tipifarnib blocks the growth of human pancreatic adenocarcinoma cell lines; this growth inhibition is related to regulation in the extracellular signal-regulated kinases (ERK) and phosphorylation levels of signal transducer and activators of transcription 3 (STAT3). Venkatasubbarao, K., et al. "Farnesyl Transferase Inhibitor (R115777)-Induced Inhibition of STAT3(Tyr705) Phosphorylation in Human Pancreatic Cancer Cell Lines Require Extracellular Signal-Regulated Kinases." Cancer Res. 65: 2861-2871 (2005).
• Tipifarnib is the active ingredient in the drug sold under the trade name Zarnestra®. This drug is currently approved in at least one country for use in elderly patients with newly diagnosed poor-risk acute myeloid leukemia. NOTE: THE TIPIFARNIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT ZARNESTRA® AND IS NOT FOR HUMAN USE.
• Our tipifarnib product is the free base, whose CAS number is given above. Chemical Abstracts Service also uses another CAS number for the same compound, namely 192185-68-5, but the entry in the CAS database for 192185-68-5 does not identify the stereochemistry.
• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
• Not available in some countries; not available to some institutions; not available for some uses.

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