| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
FASN (IC50 = 42 nM and 81 nM, cellular palmitate synthesis)
TVB-3166 targets fatty acid synthase (FASN). It is a potent and selective inhibitor that binds to and inhibits the enzymatic activity of FASN. This inhibition prevents the synthesis of palmitate and other fatty acids, which are essential for cancer cell survival. By disrupting lipid biosynthesis, the compound also inhibits the PBX-AKT-mTOR and β-catenin signal transduction pathways and suppresses the expression of oncogenic effectors like c-Myc. |
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| ln Vitro |
The cellular IC50 value of TVB-3166 (0.001-10 μM) is 0.10 μM, which results in the death of CALU-6 non-small cell lung tumor cells in 24 hours [1]. TVB-3166 (0.02 or 0.20 μM; 7 days) suppresses transcriptional activity and β-catenin backlight signaling at dosage data of TVB-3166 (0.2 μM; 48 hours) [1].
In vitro, TVB-3166 has demonstrated potent anti-cancer activity. The cellular IC50 value is 0.10 µM, leading to the death of CALU-6 non-small cell lung tumor cells within 24 hours. It induces apoptosis in Calu-6 cells and 22Rv1 prostate cancer cells. The compound's activity is mediated through the inhibition of FASN and the disruption of downstream signaling pathways. |
| ln Vivo |
TVB-3166 (interface gavage; 30-100 mg/kg/day) suppresses xenograft growth [1]. In peptides, TVB-3166 (interfacial gavage; 30-100 mg/kg/day) developed at concentrations almost three times greater than in tumors. The values were 7 and 2.9 μM, respectively, in the tumor groups at 100 and 30 mg/kg [1].
In vivo, TVB-3166 has been shown to inhibit tumor growth in various mouse models. It reduces tumor growth in an OVCAR-8 mouse xenograft model and in K-Ras wild-type or mutant patient-derived xenograft (PDX) mouse models when administered orally at a dose of 60 mg/kg. The compound's plasma concentration is approximately three times higher than that in the tumor, indicating good tissue distribution. |
| Enzyme Assay |
Inhibition of de novo palmitate synthesis via fatty acid synthase (FASN) inhibition provides an unproven approach to cancer therapy with a strong biological rationale. FASN expression increases with tumor progression and associates with chemoresistance, tumor metastasis, and diminished patient survival in numerous tumor types. TVB-3166, an orally-available, reversible, potent, and selective FASN inhibitor induces apoptosis, inhibits anchorage-independent cell growth under lipid-rich conditions, and inhibits in-vivo xenograft tumor growth. Dose-dependent effects are observed between 20-200 nM TVB-3166, which agrees with the IC50 in biochemical FASN and cellular palmitate synthesis assays. Mechanistic studies show that FASN inhibition disrupts lipid raft architecture, inhibits biological pathways such as lipid biosynthesis, PI3K-AKT-mTOR and β-catenin signal transduction, and inhibits expression of oncogenic effectors such as c-Myc; effects that are tumor-cell specific[1].
In vitro enzyme or receptor binding (non-cell) assays for TVB-3166 involve measuring its direct inhibition of FASN enzymatic activity. The assay uses a purified recombinant FASN enzyme and a fluorescent or radiolabeled substrate to measure the rate of fatty acid synthesis. The compound is incubated with the enzyme and substrate, and the decrease in product formation is measured to determine the IC50. |
| Cell Assay |
Cell Proliferation Analysis [1]
Cell Types: CALU- 6 tumor cells Tested Concentrations: 0.001, 0.01, 0.1, 1, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Caused death of CALU-6 non-small cell lung tumor cells, cell IC50 value is 0.10 μM. Cell viability assay [1] Cell Types: 90 different tumor cell lines (such as CALU-6 NSCLC cell line, NCI-H1975 NSCLC cell line) Tested Concentrations: 0.02 or 0.20 μM Incubation Duration: 7 days Experimental Results: Dose dependence of cells Induction of death was observed in all tumor cell lines. Western Blot Analysis[1] Cell Types: COLO-205 and A549 Cell Tested Concentrations: 0.2 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibition of β-catenin pathway signal transduction and transcriptional activity. In vitro cell-based assays for TVB-3166 are performed using cancer cell lines, such as Calu-6 and 22Rv1. Cells are treated with the compound, and cell viability, proliferation, and apoptosis are assessed using standard assays. Palmitate synthesis is measured by incorporating radiolabeled acetate into lipids. The compound's effects on signaling pathways like AKT-mTOR and β-catenin are analyzed by Western blotting. |
| Animal Protocol |
Animal/Disease Models: Female BALB-c-nude mice [1]
Doses: 30, 60 or 100 mg/kg Route of Administration: po (oral gavage); one time/day Experimental Results: Inhibition of the growth of xenograft tumors. Animal/Disease Models: Female BALB-c-nude mice [1] Doses: 30, 60 or 100 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: po (oral gavage); one time/day Experimental Results: The concentration in plasma is higher than that in tumor The concentration is about 3 times higher. Plasma and tumor concentrations were 7 and 2.9 μM in the 100 and 30 mg/kg groups, respectively. In vivo animal experiments for TVB-3166 are conducted using mouse xenograft models of cancer. Mice bearing subcutaneous tumors are treated orally with the compound, and tumor volume is measured over time. The compound is administered at doses of 30-100 mg/kg, and its effects on tumor growth and survival are evaluated. Plasma and tumor concentrations are measured to assess drug distribution. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TVB-3166 indicate it is orally available and well-tolerated. The compound has a molecular weight of 426.51. It is designed to achieve sufficient concentrations in the tumor tissue to inhibit FASN activity. Specific PK parameters, such as half-life and bioavailability, are determined in preclinical studies via LC-MS/MS analysis of plasma samples.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for TVB-3166 are being evaluated in preclinical studies. As a FASN inhibitor, its safety profile is important for its development as a therapeutic agent. The compound is generally well-tolerated at therapeutic doses. Its effects on normal lipid metabolism are being carefully evaluated.
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| References | |
| Additional Infomation |
Other information: TVB-3166 is a research compound being developed as a potential anti-cancer agent. It has also been assessed for its ability to inhibit SARS-CoV-2-mNG infection with an EC50 of 11 nM. The compound is available from chemical suppliers for preclinical research purposes.
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| Molecular Formula |
C24H24N4O
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|---|---|
| Molecular Weight |
384.473565101624
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| Exact Mass |
384.195
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| Elemental Analysis |
C, 74.97; H, 6.29; N, 14.57; O, 4.16
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| CAS # |
1533438-83-3
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| Related CAS # |
1533438-83-3
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| PubChem CID |
72947731
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
643
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=C(C2C(C)=C(C)NN=2)C(C)=CC=1C)N1CC(C2C=CC(C#N)=CC=2)C1
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| InChi Key |
ICDQFUFDAFKCAX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O/c1-14-9-15(2)22(10-21(14)23-16(3)17(4)26-27-23)24(29)28-12-20(13-28)19-7-5-18(11-25)6-8-19/h5-10,20H,12-13H2,1-4H3,(H,26,27)
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| Chemical Name |
4-{1-[5-(4,5-Dimethyl-2H-pyrazol-3-yl)-2,4-dimethyl-benzoyl]-azetidin-3-yl}-benzonitrile InChi Key
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| Synonyms |
TVB-3166; TVB 3166; TVB3166.
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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) |
DMSO : ~62.5 mg/mL (~162.56 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.41 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 20.8 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: 2.08 mg/mL (5.41 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (5.41 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 | 2.6010 mL | 13.0049 mL | 26.0098 mL | |
| 5 mM | 0.5202 mL | 2.6010 mL | 5.2020 mL | |
| 10 mM | 0.2601 mL | 1.3005 mL | 2.6010 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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