TVB-3166
目录号 : GC38710
A FASN inhibitor
Cas No.:1533438-83-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
TVB-3166 is an inhibitor of fatty acid synthase (FASN; IC50 = 0.042 ?M).1 It inhibits the biosynthesis of palmitate in Calu-6 non-small cell lung cancer (NSCLC) cells and MRC-5 lung fibroblasts in a concentration-dependent manner. TVB-3166 (0.2 ?M) induces apoptosis in Calu-6, as well as 22Rv1 prostate cancer, cells. It reduces tumor growth in an OVCAR-8 mouse xenograft model and K-Ras-wild-type or -mutant patient-derived xenograft (PDX) mouse models when administered at a dose of 60 mg/kg. TVB-3166 (50 mg/kg) also reduces lung viral titers in mice infected with respiratory syncytial virus A (RSV-A).2
1.Ventura, R., Mordec, K., Waszczuk, J., et al.Inhibition of de novo palmitate synthesis by fatty acid synthase induces apoptosis in tumor cells by remodeling cell membranes, inhibiting signaling pathways, and reprogramming gene expressionEBioMedicine2(8)808-824(2015) 2.Ohol, Y.M., Wang, Z., Kemble, G., et al.Direct inhibition of cellular fatty acid synthase impairs replication of respiratory syncytial virus and other respiratory virusesPLoS One10(12)e0144648(2015)
| Cas No. | 1533438-83-3 | SDF | |
| Canonical SMILES | N#CC1=CC=C(C2CN(C(C3=CC(C4=NNC(C)=C4C)=C(C)C=C3C)=O)C2)C=C1. | ||
| 分子式 | C24H24N4O | 分子量 | 384.47 |
| 溶解度 | DMSO: 62.5 mg/mL (162.56 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.601 mL | 13.0049 mL | 26.0098 mL |
| 5 mM | 0.5202 mL | 2.601 mL | 5.202 mL |
| 10 mM | 0.2601 mL | 1.3005 mL | 2.601 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
FASN inhibitor TVB-3166 prevents S-acylation of the spike protein of human coronaviruses
J Lipid Res 2022 Sep;63(9):100256.PMID:35921881DOI:10.1016/j.jlr.2022.100256.
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses mediates host cell entry and is S-acylated on multiple phylogenetically conserved cysteine residues. Multiple protein acyltransferase enzymes have been reported to post-translationally modify spike proteins; however, strategies to exploit this modification are lacking. Using resin-assisted capture MS, we demonstrate that the spike protein is S-acylated in SARS-CoV-2-infected human and monkey epithelial cells. We further show that increased abundance of the acyltransferase ZDHHC5 associates with increased S-acylation of the spike protein, whereas ZDHHC5 knockout cells had a 40% reduction in the incorporation of an alkynyl-palmitate using click chemistry detection. We also found that the S-acylation of the spike protein is not limited to palmitate, as clickable versions of myristate and stearate were also labelled the protein. Yet, we observed that ZDHHC5 was only modified when incubated with alkyne-palmitate, suggesting it has specificity for this acyl-CoA, and that other ZDHHC enzymes may use additional fatty acids to modify the spike protein. Since multiple ZDHHC isoforms may modify the spike protein, we also examined the ability of the FASN inhibitor TVB-3166 to prevent S-acylation of the spike proteins of SARS-CoV-2 and human CoV-229E. We show that treating cells with TVB-3166 inhibited S-acylation of expressed spike proteins and attenuated the ability of SARS-CoV-2 and human CoV-229E to spread in vitro. Our findings further substantiate the necessity of CoV spike protein S-acylation and demonstrate that de novo fatty acid synthesis is critical for the proper S-acylation of the spike protein.
Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines
Arch Oral Biol 2020 May;113:104707.PMID:32197133DOI:10.1016/j.archoralbio.2020.104707.
Objective: Fatty acid synthase (FASN) is overexpressed in several human cancers, including oral squamous cell carcinoma (OSCC). TVB-3166 is a recently described FASN inhibitor with antitumor effects and potential clinical relevance. The objective of this study was to evaluate the effects of TVB-3166 on OSCC cell lines. Materials and methods: The OSCC cell line SCC-9 modified to express ZsGreen (ZsG) (SCC-9 ZsG) and its in vivo selected metastatic derivative LN-1A were used to evaluate anticancer properties of TVB-3166. Cell viability was determined using MTT assays and proliferation determined by cell counting in a Neubauer chamber. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and PI staining, respectively. Cell migration was assayed by scratch assays and cell adhesion using myogel. Production of FASN, p-AKT, CPT1-α, and epithelial-mesenchymal transition (EMT) markers were examined by Western blotting. Results: TVB-3166 significantly reduced cell viability and proliferation, promoted cell cycle arrest and apoptosis, and increased adhesion to myogel in both OSCC cell lines. Finally, the drug reduced SCC-9 ZsG migration. Conclusion: Our results demonstrated that TVB-3166 has anticancer effects on both SCC-9 ZsG and its metastatic version LN-1A, which are worthy of investigation in preclinical models for OSCC.
FASN inhibition as a potential treatment for endocrine-resistant breast cancer
Breast Cancer Res Treat 2021 Jun;187(2):375-386.PMID:33893909DOI:10.1007/s10549-021-06231-6.
Purpose: The majority of breast cancers are estrogen receptor (ERα) positive making endocrine therapy a mainstay for these patients. Unfortunately, resistance to endocrine therapy is a common occurrence. Fatty acid synthase (FASN) is a key enzyme in lipid biosynthesis and its expression is commensurate with tumor grade and resistance to numerous therapies. Methods: The effect of the FASN inhibitor TVB-3166 on ERα expression and cell growth was characterized in tamoxifen-resistant cell lines, xenografts, and patient explants. Subcellular localization of ERα was assessed using subcellular fractionations. Palmitoylation and ubiquitination of ERα were assessed by immunoprecipitation. ERα and p-eIF2α protein levels were analyzed by Western blotting after treatment with TVB-3166 with or without the addition of palmitate or BAPTA. Results: TVB-3166 treatment leads to a marked inhibition of proliferation in tamoxifen-resistant cells compared to the parental cells. Additionally, TVB-3166 significantly inhibited tamoxifen-resistant breast tumor growth in mice and decreased proliferation of primary tumor explants compared to untreated controls. FASN inhibition significantly reduced ERα levels most prominently in endocrine-resistant cells and altered its subcellular localization. Furthermore, we showed that the reduction of ERα expression upon TVB-3166 treatment is mediated through the induction of endoplasmic reticulum stress. Conclusion: Our preclinical data provide evidence that FASN inhibition by TVB-3166 presents a promising therapeutic strategy for the treatment of endocrine-resistant breast cancer. Further clinical development of FASN inhibitors for endocrine-resistant breast cancer should be considered.
Direct Inhibition of Cellular Fatty Acid Synthase Impairs Replication of Respiratory Syncytial Virus and Other Respiratory Viruses
PLoS One 2015 Dec 11;10(12):e0144648.PMID:26659560DOI:10.1371/journal.pone.0144648.
Fatty acid synthase (FASN) catalyzes the de novo synthesis of palmitate, a fatty acid utilized for synthesis of more complex fatty acids, plasma membrane structure, and post-translational palmitoylation of host and viral proteins. We have developed a potent inhibitor of FASN (TVB-3166) that reduces the production of respiratory syncytial virus (RSV) progeny in vitro from infected human lung epithelial cells (A549) and in vivo from mice challenged intranasally with RSV. Addition of TVB-3166 to the culture medium of RSV-infected A549 cells reduces viral spread without inducing cytopathic effects. The antiviral effect of the FASN inhibitor is a direct consequence of reducing de novo palmitate synthesis; similar doses are required for both antiviral activity and inhibition of palmitate production, and the addition of exogenous palmitate to TVB-3166-treated cells restores RSV production. TVB-3166 has minimal effect on RSV entry but significantly reduces viral RNA replication, protein levels, viral particle formation and infectivity of released viral particles. TVB-3166 substantially impacts viral replication, reducing production of infectious progeny 250-fold. In vivo, oral administration of TVB-3166 to RSV-A (Long)-infected BALB/c mice on normal chow, starting either on the day of infection or one day post-infection, reduces RSV lung titers 21-fold and 9-fold respectively. Further, TVB-3166 also inhibits the production of RSV B, human parainfluenza 3 (PIV3), and human rhinovirus 16 (HRV16) progeny from A549, HEp2 and HeLa cells respectively. Thus, inhibition of FASN and palmitate synthesis by TVB-3166 significantly reduces RSV progeny both in vitro and in vivo and has broad-spectrum activity against other respiratory viruses. FASN inhibition may alter the composition of regions of the host cell membrane where RSV assembly or replication occurs, or change the membrane composition of RSV progeny particles, decreasing their infectivity.
Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors
Breast Cancer (Auckl) 2022 Aug 22;16:11782234221111374.PMID:36035625DOI:10.1177/11782234221111374.
Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element-binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody. Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter. Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer.