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Purity: ≥98%
TVB-3166 is a novel, potent, orally bioavailable, reversible and selective inhibitor of fatty acid synthase (FASN) inhibitor (IC50s of 42 nM and 81 nM in biochemical and cellular assay, respectively. ), it acts by inducing apoptosis, inhibiting anchorage-independent cell growth under lipid-rich conditions, and inhibiting in-vivo xenograft tumor growth.
| Targets |
FASN (IC50 = 42 nM and 81 nM, cellular palmitate synthesis)
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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].
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| 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].
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| 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].
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| 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. |
| 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. |
| References |
| 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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