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Tipifarnib

Cat. No. M1885
Tipifarnib Structure
Synonym:

R115777

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mM*1mL in DMSO USD 99  USD110 In stock
2mg USD 49.5  USD55 In stock
5mg USD 90  USD100 In stock
10mg USD 162  USD180 In stock
100mg USD 792  USD880 In stock
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Quality Control
Biological Activity

Tipifarnib (trade name Zarnestra) is a potent and selective farnesyltransferase inhibitor with IC50 of 0.6 nM. Tipifarnib (R115777) inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis. Tipifarnib exerts selective in vitro toxicity against clonal MDS hematopoiesis at concentrations less than 10 nM the effect being more prominent in white cell progenitors. R115777 results in Ki-67 value of 67.3% in vivo.

Product Citations
Customer Product Validations & Biological Datas
Source Universitatsmedizin Berlin (2020 Dec), Figure 4, Tipifarnib (AbMole Bioscience)
Method -
Cell Lines Vier Zelllinien maligner hamatologischer Erkrankungen (K562, Mec1, RC-K8 und SD-1)
Concentrations 10-8 M, 10-7 M, 10-6 M, 10-5 M
Incubation Time 24, 48, 72h
Results Zusätzlich war nach Behandlung mit ABT-199, Gefitinib, Ibrutinib und Tipifarnib ebenfalls ein Anstieg der CD150-Expression und nach Behandlung mit Ibrutinib und Tipifarnib ein Anstieg der CD133-Expression festzustellen.
Protocol
Cell Experiment
Cell lines MCF-7 cells line
Preparation method 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.
Concentrations 0~1000 nM
Incubation time 96 h
Animal Experiment
Animal models MCF-7 xenografts in Female ovariectomized Ncr foxhead nude mice
Formulation 20% w/v β-cyclodextrin (pH 2.5)
Dosages 50 mg/kg twice daily for 5 consecutive days followed by a 2-day rest period, for a total of 19 days
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 489.39
Formula C27H22Cl2N4O
CAS Number 192185-72-1
Purity 100.0%
Solubility DMSO 14 mg/mL
Storage at -20°C
References

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.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Tipifarnib, R115777 supplier, Transferase, inhibitors

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