GNF-5837Pan-Trk inhibitor CAS# 1033769-28-6 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1033769-28-6 | SDF | Download SDF |
| PubChem ID | 59397065 | Appearance | Powder |
| Formula | C28H21F4N5O2 | M.Wt | 535.49 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 32 mg/mL (59.76 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-methyl-3-[[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-6-yl]amino]phenyl]urea | ||
| SMILES | CC1=C(C=C(C=C1)NC(=O)NC2=C(C=CC(=C2)C(F)(F)F)F)NC3=CC4=C(C=C3)C(=CC5=CC=CN5)C(=O)N4 | ||
| Standard InChIKey | YYDUWLSETXNJJT-MTJSOVHGSA-N | ||
| Standard InChI | InChI=1S/C28H21F4N5O2/c1-15-4-6-19(35-27(39)37-25-11-16(28(30,31)32)5-9-22(25)29)13-23(15)34-18-7-8-20-21(12-17-3-2-10-33-17)26(38)36-24(20)14-18/h2-14,33-34H,1H3,(H,36,38)(H2,35,37,39)/b21-12- | ||
| 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 pan-Trk inhibitor. Displays antiproliferative effects in cellular Ba/F3 assays (IC50 values are 7, 9 and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively). Exhibits selectivity for Trk receptors over a range of kinases, with some activity at PDGFR and c-Kit (IC50 values are 0.87 and 0.91 μM respectively). Orally bioavailable. |
GNF-5837 Dilution Calculator
GNF-5837 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.8674 mL | 9.3372 mL | 18.6745 mL | 37.349 mL | 46.6862 mL |
| 5 mM | 0.3735 mL | 1.8674 mL | 3.7349 mL | 7.4698 mL | 9.3372 mL |
| 10 mM | 0.1867 mL | 0.9337 mL | 1.8674 mL | 3.7349 mL | 4.6686 mL |
| 50 mM | 0.0373 mL | 0.1867 mL | 0.3735 mL | 0.747 mL | 0.9337 mL |
| 100 mM | 0.0187 mL | 0.0934 mL | 0.1867 mL | 0.3735 mL | 0.4669 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: A potent and selective pan-TRK inhibitor, suppressing the activity of TrkA and TrkB with IC50 of 8 and 12 nM, respectively.
GNF-5837 is reported to selectively suppress pan-TRK potently in an oral-bioavailable manner. Neurotrophins and their receptors (TRKs) are important in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors. The TRK-inhibiting properties of GNF-5837 therefore make it a useful tool to investigate TRK biology in cancer and other non-oncology indications. [1]
In vitro: The anti-TRKA activity of GNF-5837 was detected in Ba/F3 and RIE cells expressing both TRKA and NGF. In Ba/F3 cells, this compound exhibited intensively anti-proliferation activity with an IC50 of 0.042 μM. RIE cells expressing TRKA and NGF could only survive under low attachment condition and were resistant to detachment-induced apoptosis. GNF-5837 seemed to suppress cell growth and proliferation of RIE cells intensively with an IC50 of 0.017 μM. Moreover, GNF-5837 is reported to show inhibitory effects on c-Kit and PDGFR in Mo7e cells and Rat-A10 cells, respectively. [1]
In vivo: Mice models with tumor xenografts derived from RIE cells expressing both TRKA and NGF were established in one study. GNF-5837 was then administered at ascending doses once daily to these mice for 10 days, with the aim to investigate the in vivo efficacy of GNF-5837. 72 and 100% tumor inhibition was reported at the dose of 50 and 100 mg/kg, respectively. At 25 mg/kg, only partial tumor growth inhibition was observed. [1]
Clinical trial: So far, no clinical trial has been conducted.
Reference:
[1] Albaugh F, Fan Y, Mi Y, Sun FX, Adrian F, Li NX, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu GX, Huang SL, Liu ZS, Loren J, Tuntland T, Karanewsky DS, Seidel HM and Molteni V. Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models. ACS Med. Chem. Lett. 2012. 3: 1405.
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Albumin hybrid nanoparticles loaded with tyrosine kinase A inhibitor GNF-5837 for targeted inhibition of breast cancer cell growth and invasion.[Pubmed:27793712]
Int J Pharm. 2016 Dec 30;515(1-2):527-534.
Novel albumin hybrid nanoparticles (Alb-HNPs) loaded with tyrosine kinase A (TrkA) inhibitor GNF-5837 were prepared and evaluated for antineoplastic efficacy in a panel of breast cancer cell lines. The nanomedicines (GNF-Alb-HNPs, hydrodynamic diameter approximately 150nm) were formed through a unique polyelectrolyte complexation process where albumin and GNF-5837 were encapsulated by a stabilizing layer of oppositely charged chitosan and dextran sulfate polysaccharides. GNF-Alb-HNPs showed an excellent colloidal stability and a sustained drug release over more than 24h. We found that these nanomedicines inhibited TrkA phosphorylation and downstream mitogen-activated protein kinase (MAPK) signaling in breast cancer cells specifically, resulting in anti-proliferative and pro-apoptotic effects. Moreover, the migration and invasion activities of cancer cells were dramatically suppressed and the inhibitory effects were much more prominent with GNF-Alb-HNPS than the drug alone. These results show that the GNF-Alb-HNPs may represent a novel approach for targeted breast cancer therapy.
Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.[Pubmed:24900443]
ACS Med Chem Lett. 2012 Jan 1;3(2):140-5.
Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.
