product name FTI 277 HCl
Description: FTI 277 HCl, the methyl ester of FTI 277, is a peptide mimetic of the COOH-terminal Cys-Val-Ile-Met of K-Ras4B which is a potent and selective farnesyltransferase (FTase) inhibitor with IC50 of 500 pM, it is about 100-fold selectivity over the closely related GGTase I. FTI-277 inhibits the processing of both oncogenic and normal Ras. FTI-277 was extremely potent (IC50 = 100 nM) at inhibiting H-Ras, but not the geranylgeranylated Rap1A processing in whole cells.
References: J Biol Chem. 1995 Nov 10;270(45):26802-6; Cancer Res. 1996 Apr 15;56(8):1727-30; J Clin Invest. 2003 Aug;112(3):407-14.
484.07
Formula
C22H30ClN3O3S2
CAS No.
180977-34-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 96 mg/mL (198.3 mM)
Water: 17 mg/mL (35.1 mM)
Ethanol: 14 mg/mL (28.9 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: FTI-277 inhibits Ras processing with an IC50 of 100 nM, but not the geranylgeranylated Rap1A processing in whole cells. FTI-277 induces accumulation of cytoplasmic non-farnesylated H-Ras, accumulates inactive Ras/Raf complexes in the cytoplasm, and blocks constitutive MAPK activation in H-RasF cells. FTI-277 causes increased apoptosis after irradiation and increases radiosensitivity in H-ras-transformed rat embryo cells. FTI-277 also inhibits cell growth and induces apoptosis in drug-resistant myeloma tumor cells. In SH-SY5Y cells, FTI-277 diminishes the toxic effects of methamphetamine on induction in cell degeneration, activation in c-Jun-N-terminal kinase cascades, and Ras activation. Kinase Assay: FTase and GGTase I activities from 60,000×g supernatants of human Burkitt lymphoma (Daudi) cells are assayed. Inhibition studies are performed by determining the ability of Ras CAAX peptidomimetics to inhibit the transfer of [3H]farnesyl and [3H]geranylgeranyl from [3H]farnesylpyrophosphate and [3H]geranylgeranylpyrophosphate to H-Ras-CVLS and H-Ras-CVLL, respectively. Cell Assay: Cells (8226, U266, and H929 multiple myeloma cell lines) are seeded at 8000–14 000 cells/well in 96-well plates. To establish a dose–response to FTI-277, cells are incubated for 96 h in two-fold serial dilutions ranging from 3.75 times 10-7 M to 1 times 10-5 M. Following continuous drug exposure, 50 μL MTT dye is added. The insoluble formazan complex is solubilized with DMSO and absorbance measured at 540 nm. IC50s and 95% confidence intervals are calculated by regression analysis of the linear portion of the dose–response curve. |
|---|---|
| In Vivo | In mice coinfected with hepatitis B virus (HBV) and HDV, FTI-277 (50 mg/kg/d i.p.) effectively clears HDV viremia. |
| Animal model | HBV/HDV-transgenic FVB mice |
| Formulation & Dosage | Dissolved in 5% DMSO, 0.5 mM DTT in sterile saline; 50 mg/kg; i.p. injection |
| References | J Biol Chem. 1995 Nov 10;270(45):26802-6; Cancer Res. 1996 Apr 15;56(8):1727-30; J Clin Invest. 2003 Aug;112(3):407-14. |
