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| 25mg |
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Purity: ≥98%
FTI-2148, a RAS C-terminal mimetic, is a novel, potent and highly selective dual inhibitor of farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) with IC50s of 1.4 nM and 1.7 μM, respectively. It has potential antitumor activity. FTI-2148 suppressed the growth of the human lung adenocarcinoma A-549 cells in nude mice by 33, 67, and 91% in a dose-dependent manner. Combination therapy of FTI-2148 with either cisplatin, gemcitabine, or Taxol resulted in a greater antitumor efficacy than monotherapy.
| ln Vitro |
FTI-2148 (30 μM) in NIH3T3 cells transformed with all 3 RAS reduces the farnesylation of the single farnesylated protein, HDJ2 [1]. With respect to P. falciparum PFT, mammalian PFT, and mammalian PGGT-I, FTI-2148 has an IC50 value of 15 nM, 0.82 nM, and 1700 nM, respectively. Geranylgeranyl transferase-I is known as PGGT-I and protein farnesyl transferase (PFT)[2].
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| ln Vivo |
In a mouse model of human lung adenocarcinoma A-549 cells grown 91%, FTI-2148 (ip; 25 or 50 mpk/day using minipump; start on day 15, halt on day 45, restart on days 53-83) suppresses tumors. In a human xenograft nude mouse model, FTI-2148 (subcutaneous injection; 25 mpk/day using minipump; 14 days) reduced tumor development by 77% at the conclusion of two weeks of treatment [1]. In a ras transgenic mouse model, FTI-2148 (subcutaneous injection; 100 mg/kg/day; 14 days) promotes breast tumor regression [1]. In mouse mammary tumors cultured in vivo, FTI-2148 (subcutaneous injection; 100 mg/kg/day; 4 days) suppresses 85-88% of FTase activity but not GGTase I enzyme activity [3].
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| Cell Assay |
Western Blot Analysis[]
Cell Types: NIH3T3 cells transformed with KRAS HRAS and NRAS Tested Concentrations: 30 μM Incubation Duration: Experimental Results: Inhibition of prenylation of KRAS and NRAS. |
| Animal Protocol |
Animal/Disease Models: Ras transgenic mouse model [3]
Doses: 100 mg/kg/day Route of Administration: subcutaneous injection; 100 mg/kg/day; 14 days Experimental Results: Induced 87 ± 3% of breast cancer regression in mice. |
| References |
[1]. Sun J, et al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine.Cancer Res. 1999 Oc
[2]. Carrico D, et al.In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability.Bioorg Med Chem. 2004 Dec 15;12(24):6517-26. [3]. Sun J, et al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice.Cancer Res. 2003 Dec 15;63(24):8922-9. |
| Molecular Formula |
C24H28N4O3S
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|---|---|
| Molecular Weight |
452.56912
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| CAS # |
251577-09-0
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| Related CAS # |
FTI-2148 diTFA;817586-01-9
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| SMILES |
CSCC[C@H](NC(C1=CC=C(C=C1C2=CC=CC=C2C)CNCC3=CNC=N3)=O)C(O)=O
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| InChi Key |
KULAYTGUTXCHSV-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C24H28N4O3S/c1-16-5-3-4-6-19(16)21-11-17(12-25-13-18-14-26-15-27-18)7-8-20(21)23(29)28-22(24(30)31)9-10-32-2/h3-8,11,14-15,22,25H,9-10,12-13H2,1-2H3,(H,26,27)(H,28,29)(H,30,31)/t22-/m0/s1
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| Chemical Name |
(5-((((1H-imidazol-4-yl)methyl)amino)methyl)-2'-methyl-[1,1'-biphenyl]-2-carbonyl)-L-methionine
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| Synonyms |
FTI2148 FTI 2148 FTI-2148 FTI-2148 TFA FTI-2148 trfluoroacetic acid salt FTI-2148 free base
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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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2096 mL | 11.0480 mL | 22.0960 mL | |
| 5 mM | 0.4419 mL | 2.2096 mL | 4.4192 mL | |
| 10 mM | 0.2210 mL | 1.1048 mL | 2.2096 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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