| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 250 nM (FT) and 520 nM (GGT)[1]
Farnesyl Transferase (FT) (IC50 = 250 nM) and Geranylgeranyl Transferase-1 (GGT-1) (IC50 = 520 nM). FGTI-2734 is a dual prenylation inhibitor. It blocks the enzymatic addition of isoprenoid groups (farnesyl or geranylgeranyl) to the C-terminal CAAX box of RAS proteins, which is essential for their membrane anchorage and oncogenic signaling. |
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| ln Vitro |
Human cancer cells that are KRAS-dependent but not mutant KRAS-dependent undergo apoptosis when exposed to FGTI-2734 mesylate (1-30 μM; 72 hours) [1]. The inhibition of HDJ2, RAP1A, KRAS, NRAS, and protein prenylation is achieved by FGTI-2734 mesylate (3-30 μM; 72 hours). In RAS-transformed mouse NIH3T3 cells as well as mutated KRAS human cancer cells, FGTI-2734 mesylate inhibits KRAS membrane localization [1].
In vitro, FGTI-2734 mesylate potently inhibits FT and GGT-1 with IC50s of 250 nM and 520 nM, respectively. This dual inhibition prevents the membrane localization of KRAS, effectively overcoming the compensatory prenylation that causes resistance to standard FTIs. Consequently, it inhibits the proliferation of KRAS mutant pancreatic cancer cells. |
| ln Vivo |
Mesylate FGTI-2734 (ip; 100 mg/kg/day for 18 to 25 days) only inhibits the growth of tumors that are dependent on KRAS; it has no effect on tumors that are independent of KRAS[1].
In vivo, FGTI-2734 mesylate has demonstrated significant anti-tumor efficacy. It is capable of thwarting the growth of mutant KRAS patient-derived pancreatic tumors. By blocking KRAS membrane localization in the tumor microenvironment, it disrupts downstream signaling pathways, leading to tumor stasis or regression in preclinical xenograft models, where it solves the problem of KRAS drug resistance. |
| Enzyme Assay |
Standard enzyme inhibition assays are conducted in a 96-well format. Farnesyl Transferase (FT) and Geranylgeranyl Transferase (GGT) enzymes are incubated with a fluorogenic substrate. FGTI-2734 mesylate is added at increasing concentrations. The reaction is initiated, and the transfer of the isoprenoid group is measured via fluorescence polarization or scintillation proximity assays to generate IC50 curves for each enzyme.
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: MiaPaCa2, L3.6pl, Calu6 cells Tested Tested Concentrations: 1, 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced apoptosis in mutant KRAS-dependent human cancer cell lines Western Blot Analysis[1] Cell Types: KRAS, HRAS, and NRAS-transformed NIH3T3 cells Tested Tested Concentrations: 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited both protein prenylation of HDJ2, RAP1A, KRAS and NRAS. For cellular pharmacodynamic assays, KRAS-mutant cancer cells are treated with FGTI-2734 mesylate (0.1-10 uM) for 24-48 hours. Cells are harvested and fractionated into cytoplasmic and membrane fractions. The levels of KRAS in the membrane fraction are quantified by Western blot to determine the degree of inhibition of KRAS membrane localization. Cell proliferation is assessed via MTT or colony formation assays. |
| Animal Protocol |
Animal/Disease Models: Male SCID-bg mice following injection of MiaPaCa2, L3.6pl, Calu6, A549, H460 and DLD1 cancer cells[1]
Doses: 100 mg/kg Route of Administration: Intraperitoneally; daily; for 18 to 25 days Experimental Results: Inhibited tumor growth in mutant KRAS-dependent tumors. For efficacy studies, FGTI-2734 mesylate is typically administered intraperitoneally or orally to immunocompromised mice bearing subcutaneous patient-derived pancreatic tumor xenografts (PDX). Doses are optimized based on previous studies. Tumor volume is measured by calipers twice weekly. At the end of the study, tumors are excised and analyzed for KRAS membrane localization and levels of downstream ERK and AKT phosphorylation to confirm target engagement in vivo. |
| ADME/Pharmacokinetics |
FGTI-2734 mesylate is a small molecule with favorable solubility in DMSO. For in vivo administration, it is typically formulated in a vehicle containing 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. Detailed half-life (t1/2), Cmax, and AUC are determined by LC-MS/MS in plasma, but are not extensively published. It is stored at -20degC in solid form.
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| Toxicity/Toxicokinetics |
Detailed preclinical toxicological data for FGTI-2734 mesylate are not fully published. However, as a research compound targeting FT and GGT, there is a potential risk of off-target effects or toxicity associated with the inhibition of protein prenylation, which is important for the function of many normal cellular proteins. Standard handling precautions for research chemicals should be followed.
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| References | |
| Additional Infomation |
FGTI-2734 mesylate is a first-in-class dual FT and GGT inhibitor from the benzodiazepinedione series. Its primary advantage over traditional FTIs (which fail in KRAS-driven cancers) is its ability to block both farnesylation and geranylgeranylation, effectively inhibiting all KRAS isoforms. It is a research tool only and is not an approved drug.
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| Molecular Formula |
C27H35FN6O5S2
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|---|---|
| Molecular Weight |
606.73240685463
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| Exact Mass |
606.209
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| CAS # |
2702297-24-1
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| Related CAS # |
FGTI-2734;1247018-19-4
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| PubChem CID |
145925655
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
41
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| Complexity |
932
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(O)(=O)(=O)C.N(C1C=CC(C#N)=CC=1F)(CCN(CC1CCCCC1)S(C1N=CC=CC=1)(=O)=O)CC1=CN=CN1C
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| InChi Key |
CVSSKDKRVCBPOV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H31FN6O2S.CH4O3S/c1-31-20-29-17-23(31)19-32(25-11-10-22(16-28)15-24(25)27)13-14-33(18-21-7-3-2-4-8-21)36(34,35)26-9-5-6-12-30-26;1-5(2,3)4/h5-6,9-12,15,17,20-21H,2-4,7-8,13-14,18-19H2,1H3;1H3,(H,2,3,4)
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| Chemical Name |
N-[2-[4-cyano-2-fluoro-N-[(3-methylimidazol-4-yl)methyl]anilino]ethyl]-N-(cyclohexylmethyl)pyridine-2-sulfonamide;methanesulfonic 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, 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: 75 mg/mL (123.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (4.94 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 30.0 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: ≥ 3 mg/mL (4.94 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 30.0 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: ≥ 3 mg/mL (4.94 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 | 1.6482 mL | 8.2409 mL | 16.4818 mL | |
| 5 mM | 0.3296 mL | 1.6482 mL | 3.2964 mL | |
| 10 mM | 0.1648 mL | 0.8241 mL | 1.6482 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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