| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
FTI-2148 targets farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1), key enzymes in the post-translational modification of proteins through prenylation. By inhibiting FT-1 and GGT-1, it prevents the prenylation of proteins such as RAS, which is critical for their membrane localization and function. The compound shows a high degree of selectivity, with an IC50 of 1.4 nM for FT-1 and 1.7 μM for GGT-1. It also inhibits P. falciparum protein farnesyltransferase (PFT) with an IC50 of 15 nM and mammalian PFT with an IC50 of 0.82 nM.
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| 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].
In vitro, FTI-2148 (30 μM) inhibits the farnesylation of the exclusively farnesylated protein HDJ2 in all three RAS-transformed NIH3T3 cells. It also inhibits the prenylation of KRAS and NRAS in these cell lines. The compound is effective against P. falciparum PFT, Mammalian PFT, and Mammalian PGGT-I with IC50 values of 15 nM, 0.82 nM, and 1700 nM, respectively. These findings confirm its potent and selective inhibition of farnesyltransferase activity in cellular models. |
| 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].
In vivo, FTI-2148 has demonstrated significant antitumor efficacy. In a human lung adenocarcinoma A-549 xenograft mouse model, intraperitoneal injection at 25 or 50 mg/kg/day inhibited tumor growth by 91%. In a human xenograft nude mouse model, subcutaneous injection at 25 mg/kg/day for 14 days inhibited tumor growth by 77%. In a ras transgenic mouse model, subcutaneous injection at 100 mg/kg/day for 14 days induced breast tumor regression by 87 ± 3%. The compound also resulted in 85-88% inhibition of FTase with no inhibition of GGTase I in breast tumors. |
| Enzyme Assay |
In vitro enzyme assays for FTI-2148 typically involve measuring the inhibition of farnesyltransferase and geranylgeranyltransferase activity using purified enzyme preparations. The compound is incubated with the enzyme, its substrate (e.g., farnesyl pyrophosphate), and a peptide substrate representing the CAAX motif of a target protein. The transfer of the prenyl group to the peptide is measured using radiometric or fluorescence-based detection methods. The IC50 values are determined from dose-response curves.
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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. In vitro cell-based assays for FTI-2148 involve treating RAS-transformed NIH3T3 cells with the compound at 30 μM. The inhibition of protein farnesylation is assessed by measuring the prenylation status of specific proteins like HDJ2, KRAS, and NRAS using Western blot analysis. The compound's effects on cell proliferation and signaling pathways can also be studied in various cancer cell lines. |
| 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. In vivo animal experiments for FTI-2148 have been conducted in several mouse models. In human lung adenocarcinoma A-549 xenografts, the compound was administered via intraperitoneal injection using a mini-pump at 25 or 50 mg/kg/day. In human xenograft nude mouse models, it was given subcutaneously at 25 mg/kg/day for 14 days. In a ras transgenic mouse model, it was administered subcutaneously at 100 mg/kg/day for 14 days. Tumor growth inhibition and regression were the primary efficacy endpoints. |
| ADME/Pharmacokinetics |
FTI-2148 has a molecular weight of 452.57 and a molecular formula of C24H28N4O3S. It is typically dissolved in DMSO for in vitro studies and formulated for in vivo administration. Its pharmacokinetic properties, including absorption, distribution, metabolism, and elimination, have been characterized in preclinical studies. The compound is typically stored under recommended conditions, such as at -20°C, and shipped with blue ice.
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| Toxicity/Toxicokinetics |
Available toxicity data for FTI-2148 is limited to preclinical studies. The compound is generally well-tolerated at therapeutic doses in animal models. As an inhibitor of protein prenylation, its safety profile is related to its effects on this essential cellular process. Comprehensive toxicological studies would be required for therapeutic development. Standard safety precautions should be taken when handling the compound.
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| References |
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| Additional Infomation |
FTI-2148 is a potent and selective dual inhibitor of farnesyl transferase and geranylgeranyl transferase-1 with significant antitumor efficacy. It is a RAS C-terminal mimetic and a non-thiol-containing peptidomimetic. The compound has shown activity against both mammalian and P. falciparum farnesyltransferase. Its high selectivity and potent in vivo efficacy make it a valuable tool for studying protein prenylation and RAS biology in cancer research.
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| Molecular Formula |
C24H28N4O3S
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| Molecular Weight |
452.56912
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| Exact Mass |
452.188
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| CAS # |
251577-09-0
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| Related CAS # |
FTI-2148 diTFA;817586-01-9
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| PubChem CID |
9981319
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
730.1±60.0 °C at 760 mmHg
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| Flash Point |
395.4±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.626
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| LogP |
2.45
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
32
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| Complexity |
608
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1C=C(CNCC2=CC(C3C=CC=CC=3C)=C(C(NC(C(O)=O)CCSC)=O)C=C2)N=C1
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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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| HS Tariff Code |
2934.99.9001
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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 Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
| 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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