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| Targets |
FTI-2153 TFA targets farnesyltransferase (FTase), the enzyme responsible for attaching a farnesyl lipid group to the C-terminal CAAX motif of proteins such as Ras. This post-translational modification is essential for the membrane localization and function of Ras proteins, which are critical regulators of cell proliferation and survival. By inhibiting FTase, FTI-2153 TFA prevents Ras farnesylation and subsequent membrane association, thereby blocking Ras-mediated signaling pathways. The compound shows high selectivity for FTase over other prenyltransferases.
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| ln Vitro |
In two human lung cancer cell lines, FTI-2153 inhibits bipolar spindle formation during mitosis regardless of transformation and the presence of Ras and p53 mutations[2]. In both transformed and non-transformed cells, the proportion of prometaphase cells with ring-like DNA morphology is increased by FTI-2153[2]. T-24 and Calu-1 cell growth is inhibited by FTI-2153 (15 μM) by 38 and 36%, respectively. Less sensitive, NIH3T3, HFF, and HT-1080 are inhibited by only 8, 8, and 13%, in that order. The growth of A-549 and OVCAR3 cells is suppressed by 25 and 22%, respectively. FTI-2153 inhibits cell growth in both T-24 and Calu-1 cells, but it only affects Calu-1 cells' ability to form bipolar spindles. Only NIH3T3 cells are resistant to FTI-2153 inhibition of bipolar spindle formation, whereas HFF and NIH3T3 cells are resistant to FTI-2153 growth inhibition[2].
In vitro, FTI-2153 TFA demonstrates potent inhibition of FTase with an IC50 of 1.4 nM. The compound inhibits H-Ras processing with an IC50 of 10 nM, showing greater than 3000-fold selectivity over Rap1A processing. In cancer cell lines, FTI-2153 TFA exhibits anti-proliferative activity, with an IC50 of 0.1 µM in DaOY tumor cells. The compound inhibits bipolar spindle formation during mitosis independently of transformation and Ras and p53 mutation status. FTI-2153 TFA shows concentration-dependent inhibition of cell proliferation. |
| ln Vivo |
In vivo activity data for FTI-2153 TFA are limited, as the compound is primarily used in vitro. Based on its mechanism of FTase inhibition and anti-proliferative activity, the compound is expected to exhibit antitumor activity in animal models. However, detailed efficacy studies in animal models have not been extensively reported. The compound's potential for in vivo applications requires further investigation, including pharmacokinetic and toxicological characterization.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for FTI-2153 TFA typically involves measuring FTase activity using a fluorescent or radiolabeled substrate (e.g., dansyl-GCVLS or [³H]-farnesyl pyrophosphate). Purified recombinant human FTase is incubated with varying concentrations of FTI-2153 TFA (0.001-1000 nM) in assay buffer at 37°C for 30-60 minutes. The reaction is initiated by adding the substrate, and the incorporation of farnesyl groups into the substrate is quantified. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: NIH3T3, HFF, HT1080, T-24, OVCAR3, A-549 and Calu-1 CELLS. Tested Concentrations: 48 h. Incubation Duration: 15 μM. Experimental Results: When A-549 cells were treated with FTI-2153 (15 μM for 48 h) , the proportion of cells at prometaphase increased relative to the other phases of mitosis. FTI-2153 accumulated cells at prometaphase with a rosette-like morphology where chromosomes form a ring surrounding a monoaster of microtubules. In all cells, except for T-24 and NIH3T3, FTI-2153 treatment increased the proportion of mitotic cells in prometaphase and diminished the percentage of cells in telophase/cytokinesis. In HT1080 cells, the percentage of cells in prometaphase and telophase/cytokinesis were 5 and 85% in control cells and 55 and 35% in Treated cells, respectively. Similarly results were also found in HFF cells. Calu-1 and A-549 cells, as described previously, had similarly large changes, whereas OVCAR3 had smaller changes. In contrast, FTI-2153 did not Dramatically aff For in vitro cell-based assays, cancer cell lines such as DaOY, H-Ras-transformed cells, or other tumor cell lines are cultured and treated with FTI-2153 TFA at concentrations ranging from 0.01-100 µM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Ras processing is evaluated by Western blot analysis to detect unprenylated Ras. Cell cycle analysis is performed by flow cytometry. Apoptosis is assessed using Annexin V-FITC/PI staining or caspase activity assays. |
| Animal Protocol |
In vivo animal studies for FTI-2153 TFA have not been extensively reported. Based on the compound's mechanism as a FTase inhibitor, potential in vivo studies would involve administration to tumor-bearing mouse models via oral gavage, intraperitoneal injection, or intravenous injection at doses ranging from 1-50 mg/kg. Tumor growth would be monitored by caliper measurements. Ras processing and signaling would be assessed in tumor tissues by Western blot and immunohistochemistry.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of FTI-2153 TFA have not been fully characterized. The molecular weight is 580.62 g/mol and the molecular formula is C₂₇H₃₁F₃N₄O₅S. The compound should be stored as a powder at -20°C for up to 3 years and in solvent at -80°C for up to 1 year. Detailed pharmacokinetic parameters such as bioavailability, half-life, and protein binding have not been reported. Stability in solution may be limited.
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| Toxicity/Toxicokinetics |
Toxicology data for FTI-2153 TFA are limited. As a research compound, it has not been systematically evaluated for safety. The compound's mechanism of FTase inhibition suggests potential cytotoxicity, which may be desirable for anticancer applications but requires careful safety assessment. Standard toxicological endpoints including cell viability, genotoxicity, and organ toxicity should be evaluated. The compound is intended for research use only and is not approved for human use.
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| References |
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| Additional Infomation |
FTI-2153 TFA is a highly selective and potent farnesyltransferase inhibitor with an IC50 of 1.4 nM. It shows greater than 3000-fold selectivity for H-Ras processing over Rap1A processing. The compound exhibits anti-cancer activity and is used as a research tool for studying Ras signaling, protein prenylation, and cancer biology. FTI-2153 TFA is intended for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C27H31F3N4O5S
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| Molecular Weight |
580.619055986404
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| Exact Mass |
580.196
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| CAS # |
2820151-01-5
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| Related CAS # |
FTI-2153;344900-92-1
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| PubChem CID |
155981984
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
40
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| Complexity |
706
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC=CC=C1C2=C(C=CC(=C2)CNCC3=CN=CN3)C(=O)N[C@@H](CCSC)C(=O)OC.C(=O)(C(F)(F)F)O
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| InChi Key |
LRKNQRCLUQTFRP-BQAIUKQQSA-N
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| InChi Code |
InChI=1S/C25H30N4O3S.C2HF3O2/c1-17-6-4-5-7-20(17)22-12-18(13-26-14-19-15-27-16-28-19)8-9-21(22)24(30)29-23(10-11-33-3)25(31)32-2;3-2(4,5)1(6)7/h4-9,12,15-16,23,26H,10-11,13-14H2,1-3H3,(H,27,28)(H,29,30);(H,6,7)/t23-;/m0./s1
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| Chemical Name |
methyl (2S)-2-[[4-[(1H-imidazol-5-ylmethylamino)methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate;2,2,2-trifluoroacetic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO: 90 mg/mL (155.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (3.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (3.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.25 mg/mL (3.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7223 mL | 8.6115 mL | 17.2230 mL | |
| 5 mM | 0.3445 mL | 1.7223 mL | 3.4446 mL | |
| 10 mM | 0.1722 mL | 0.8611 mL | 1.7223 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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