GSK2194069human fatty acid synthase inhibitor CAS# 1332331-08-4 |
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 1332331-08-4 | SDF | Download SDF |
| PubChem ID | 67376285 | Appearance | Powder |
| Formula | C25H24N4O3 | M.Wt | 428.48 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (233.38 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-[4-(1-benzofuran-5-yl)phenyl]-3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-1H-1,2,4-triazol-5-one | ||
| SMILES | C1CC1C(=O)N2CCC(C2)CC3=NNC(=O)N3C4=CC=C(C=C4)C5=CC6=C(C=C5)OC=C6 | ||
| Standard InChIKey | AQTPWCUIYUOEMG-INIZCTEOSA-N | ||
| Standard InChI | InChI=1S/C25H24N4O3/c30-24(18-1-2-18)28-11-9-16(15-28)13-23-26-27-25(31)29(23)21-6-3-17(4-7-21)19-5-8-22-20(14-19)10-12-32-22/h3-8,10,12,14,16,18H,1-2,9,11,13,15H2,(H,27,31)/t16-/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent human fatty acid synthase (hFASN) inhibitor (IC50 = 7.7 nM); inhibits hFAS β-ketoacyl reductase activity. Inhibits lipid synthesis and attenuates proliferation of A549 non-small-cell lung cancer cells (EC50 = 15 nM) in vitro. |
GSK2194069 Dilution Calculator
GSK2194069 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.3338 mL | 11.6692 mL | 23.3383 mL | 46.6766 mL | 58.3458 mL |
| 5 mM | 0.4668 mL | 2.3338 mL | 4.6677 mL | 9.3353 mL | 11.6692 mL |
| 10 mM | 0.2334 mL | 1.1669 mL | 2.3338 mL | 4.6677 mL | 5.8346 mL |
| 50 mM | 0.0467 mL | 0.2334 mL | 0.4668 mL | 0.9335 mL | 1.1669 mL |
| 100 mM | 0.0233 mL | 0.1167 mL | 0.2334 mL | 0.4668 mL | 0.5835 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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IC50: 7.7 nM
GSK 2194069 is a potent human fatty acid synthase inhibitor.
Human fatty acid synthase (hFAS) is a multifunctional enzyme solely responsible for the de novo synthesis of long chain fatty acids. hFAS is expressed highly in a number of cancers, while with low observed expression in most normal tissues. Though normal tissues get fatty acids from the diet, tumor tissues can rely on de novo fatty acid synthesis, which makes hFAS an attractive metabolic target for cancer treatment.
In vitro: GSK2194069 displayed acceptable solubility and permeability and thus was chosen for further characterization. GSK2194069 had an IC50 of 29 ± 3.2 nM versus hFAS with acetoacetyl-CoA as the substrate but showed little or no inhibition with crotonyl-CoA andβ-hydroxybutyryl-CoA. GSK2194069 was also found not to inhibit the partial activities of the KS domain [1].
In vivo: In those mice dosed with GSK2194069, tumour growth was inhibited. There was no significant weight loss in the GSK2194069 treated group and no adverse effects were observed. The effect of GSK2194069 in decreasing acetate uptake was demonstrated by scintillation detection of C42b xenograft tumours by 56% 2 hours after dosing with GSK2194069. Inhibition of FAS caused by GSK2194069 led to a decrease in acetate signal in all animals [1].
Clinical trial: N/A
References:
[1] Hardwicke MA,Rendina AR,Williams SP,Moore ML,Wang L,Krueger JA,Plant RN,Totoritis RD,Zhang G,Briand J,Burkhart WA,Brown KK, Parrish CA. A human fatty acid synthase inhibitor binds β-ketoacyl reductase in the keto-substrate site. Nat Chem Biol.2014 Sep;10(9):774-9.
[2] Greg Shaw, David Lewis, Joan Boren, Antonio Ramos-Montoya, Robert Bielik, Dmitry Soloviev, Brindle Kevin, Neal David. 509 THERAPEUTIC FATTY ACID SYNTHASE INHIBITION IN PROSTATE CANCER AND THE USE OF 11C-ACETATE TO MONITOR THERAPEUTIC EFFECTS. The Journal of Urology. 2013Volume 189, Issue 4, Supplement, Pagese208–e209
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Molecular Pathways: Fatty Acid Synthase.[Pubmed:26519059]
Clin Cancer Res. 2015 Dec 15;21(24):5434-8.
Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer.
A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site.[Pubmed:25086508]
Nat Chem Biol. 2014 Sep;10(9):774-9.
Human fatty acid synthase (hFAS) is a complex, multifunctional enzyme that is solely responsible for the de novo synthesis of long chain fatty acids. hFAS is highly expressed in a number of cancers, with low expression observed in most normal tissues. Although normal tissues tend to obtain fatty acids from the diet, tumor tissues rely on de novo fatty acid synthesis, making hFAS an attractive metabolic target for the treatment of cancer. We describe here the identification of GSK2194069, a potent and specific inhibitor of the beta-ketoacyl reductase (KR) activity of hFAS; the characterization of its enzymatic and cellular mechanism of action; and its inhibition of human tumor cell growth. We also present the design of a new protein construct suitable for crystallography, which resulted in what is to our knowledge the first co-crystal structure of the human KR domain and includes a bound inhibitor.
