Lipofermata
(Synonyms: 5-溴-5'-苯基-3'H-螺环[吲哚啉-3,2'-[1,3,4]噻二唑]-2-酮) 目录号 : GC34647
An inhibitor of fatty acid transport
Cas No.:297180-15-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Lipofermata is an inhibitor of fatty acid transport (IC50 = 4.84 μM in Caco-2 cells).1 It inhibits uptake of long- and very long-chain, but not medium-chain, fatty acids in mmC2C12, rnINS-1E, Caco-2, and HepG2 cells (IC50s = 3-6 μM).2 Lipofermata inhibits induction of BiP and CHOP, apoptosis, and lipid droplet accumulation, as well as reduces production of reactive oxygen species (ROS) and reverses decreases in glutathione (GSH) levels induced by palmitate in HepG2 and INS-1E cells. In vivo, lipofermata (500 mg/kg) inhibits absorption of 13C-oleate in mice.
1.Sandoval, A., Chokshi, A., Jesch, E.D., et al.Identification and characterization of small compound inhibitors of human FATP2Biochem. Pharmacol.79(7)990-999(2010) 2.Ahowesso, C., Black, P.N., Saini, N., et al.Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell deathBiochem. Pharmacol.98(1)167-181(2015)
| Cas No. | 297180-15-5 | SDF | |
| 别名 | 5-溴-5'-苯基-3'H-螺环[吲哚啉-3,2'-[1,3,4]噻二唑]-2-酮 | ||
| Canonical SMILES | O=C1NC2=C(C=C(Br)C=C2)C13SC(C4=CC=CC=C4)=NN3 | ||
| 分子式 | C15H10BrN3OS | 分子量 | 360.23 |
| 溶解度 | DMSO : 100 mg/mL (277.60 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.776 mL | 13.88 mL | 27.76 mL |
| 5 mM | 0.5552 mL | 2.776 mL | 5.552 mL |
| 10 mM | 0.2776 mL | 1.388 mL | 2.776 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。
Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins
Cancer Discov 2018 Aug;8(8):1006-1025.PMID:29903879DOI:10.1158/2159-8290.CD-17-1371.
Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface. Among the six FATP/SLC27A family members, melanomas significantly overexpress FATP1/SLC27A1. Melanocyte-specific FATP1 expression cooperates with BRAFV600E in transgenic zebrafish to accelerate melanoma development, an effect that is similarly seen in mouse xenograft studies. Pharmacologic blockade of FATPs with the small-molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. These data demonstrate that stromal adipocytes can drive melanoma progression through FATP lipid transporters and represent a new target aimed at interrupting adipocyte-melanoma cross-talk.Significance: We demonstrate that stromal adipocytes are donors of lipids that mediate melanoma progression. Adipocyte-derived lipids are taken up by FATP proteins that are aberrantly expressed in melanoma. Inhibition of FATPs decreases melanoma lipid uptake, invasion, and growth. We provide a mechanism for how stromal adipocytes drive tumor progression and demonstrate a novel microenvironmental therapeutic target. Cancer Discov; 8(8); 1006-25. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 899.
Lipidomics data showing the effect of Lipofermata on myeloid-derived suppressor cells in the spleens of tumor-bearing mice
Data Brief 2021 Feb 13;35:106882.PMID:33665270DOI:10.1016/j.dib.2021.106882.
The regulation of myeloid-derived suppressor cells (MDSCs) function is key for effective tumor immunotherapy. Recent lipidomics data revealed that MDSCs accumulate lipid species thereby promote their immunosuppressive activity on T cells. However, genetic manipulation of fatty acid transport protein 2 in mice reduced lipid accumulation in polymorphonuclear MDSCs. Herein we present for the first time lipidome of splenic MDSCs from B16F10 melanoma-bearing mice treated with FATP2 inhibitor - Lipofermata compared to the control group. B16F10 were subcutaneously injected into the left flank of wild-type C57BL/6 mice, either Lipofermata or vehicle was administered to the mice every day starting from day 7 post-tumor injection for 2 weeks. CD11b+Gr1+ cells from the spleen referred to as MDSCs were sorted on a flow cytometer machine for lipid extraction. Lipid was extracted using methyl‑tert‑butyl ether as previously described with slight modification, followed by liquid chromatography-mass spectrophotometry lipid profiling using a Q-Exactive instrument coupled with HPLC. The raw scans were identified and quantified with LipidSearch while raw data for various lipid species available on the Mendeley Data repository [1]. The lipid profiles reveal change in lipid species following blockade of FATP2 expression in MDSCs compared to the control. These data were collected in connection to a co-submitted paper [2].
Fatty acid transport protein 2 interacts with ceramide synthase 2 to promote ceramide synthesis
J Biol Chem 2022 Apr;298(4):101735.PMID:35181339DOI:10.1016/j.jbc.2022.101735.
Dihydroceramide is a lipid molecule generated via the action of (dihydro)ceramide synthases (CerSs), which use two substrates, namely sphinganine and fatty acyl-CoAs. Sphinganine is generated via the sequential activity of two integral membrane proteins located in the endoplasmic reticulum. Less is known about the source of the fatty acyl-CoAs, although a number of cytosolic proteins in the pathways of acyl-CoA generation modulate ceramide synthesis via direct or indirect interaction with the CerSs. In this study, we demonstrate, by proteomic analysis of immunoprecipitated proteins, that fatty acid transporter protein 2 (FATP2) (also known as very long-chain acyl-CoA synthetase) directly interacts with CerS2 in mouse liver. Studies in cultured cells demonstrated that other members of the FATP family can also interact with CerS2, with the interaction dependent on both proteins being catalytically active. In addition, transfection of cells with FATP1, FATP2, or FATP4 increased ceramide levels although only FATP2 and 4 increased dihydroceramide levels, consistent with their known intracellular locations. Finally, we show that Lipofermata, an FATP2 inhibitor which is believed to directly impact tumor cell growth via modulation of FATP2, decreased de novo dihydroceramide synthesis, suggesting that some of the proposed therapeutic effects of Lipofermata may be mediated via (dihydro)ceramide rather than directly via acyl-CoA generation. In summary, our study reinforces the idea that manipulating the pathway of fatty acyl-CoA generation will impact a wide variety of down-stream lipids, not least the sphingolipids, which utilize two acyl-CoA moieties in the initial steps of their synthesis.
A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19
Sci Rep 2021 Jun 7;11(1):11982.PMID:34099831DOI:10.1038/s41598-021-91526-3.
In this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as Propylthiouracil, 2-Bromopalmitate, Lipofermata, Tunicamycin, Benzyl Isothiocyanate, Tipifarnib and Lonafarnib) are also proposed.
Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell death
Biochem Pharmacol 2015 Nov 1;98(1):167-81.PMID:26394026DOI:10.1016/j.bcp.2015.09.004.
Chronic elevation of plasma free fatty acid (FFA) levels is commonly associated with obesity, type 2 diabetes, cardiovascular disease and some cancers. Experimental evidence indicates FFA and their metabolites contribute to disease development through lipotoxicity. Previously, we identified a specific fatty acid transport inhibitor CB16.2, a.k.a. Lipofermata, using high throughput screening methods. In this study, efficacy of transport inhibition was measured in four cell lines that are models for myocytes (mmC2C12), pancreatic β-cells (rnINS-1E), intestinal epithelial cells (hsCaco-2), and hepatocytes (hsHepG2), as well as primary human adipocytes. The compound was effective in inhibiting uptake with IC50s between 3 and 6μM for all cell lines except human adipocytes (39μM). Inhibition was specific for long and very long chain fatty acids but had no effect on medium chain fatty acids (C6-C10), which are transported by passive diffusion. Derivatives of Lipofermata were evaluated to understand structural contributions to activity. Lipofermata prevented palmitate-mediated oxidative stress, induction of BiP and CHOP, and cell death in a dose-dependent manner in hsHepG2 and rnINS-1E cells, suggesting it will prevent induction of fatty acid-mediated cell death pathways and lipotoxic disease by channeling excess fatty acids to adipose tissue and away from liver and pancreas. Importantly, mice dosed orally with Lipofermata were not able to absorb (13)C-oleate demonstrating utility as an inhibitor of fatty acid absorption from the gut.