GNF-5837Pan-Trk inhibitor CAS# 1033769-28-6 |
- Lestaurtinib
Catalog No.:BCC2440
CAS No.:111358-88-4
- GW441756
Catalog No.:BCC5093
CAS No.:504433-23-2
- TLQP 21
Catalog No.:BCC2405
CAS No.:869988-94-3
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| 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. |
||
| 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. |
||
| 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. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
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.
- Itol A
Catalog No.:BCN5847
CAS No.:1033747-78-2
- GNE-493
Catalog No.:BCC8048
CAS No.:1033735-94-2
- 1-Methyl-L-4,5-dihydroorotic acid
Catalog No.:BCC8472
CAS No.:103365-69-1
- L-364,373
Catalog No.:BCC7445
CAS No.:103342-82-1
- 3-Oxo-4-aza-5-alpha-androstane-17β-carboxylic acid
Catalog No.:BCC8641
CAS No.:103335-55-3
- Pre-schisanartanin B
Catalog No.:BCN5846
CAS No.:1033288-92-4
- Taltirelin
Catalog No.:BCC5271
CAS No.:103300-74-9
- LDK378
Catalog No.:BCC3691
CAS No.:1032900-25-6
- GSK1292263
Catalog No.:BCC3786
CAS No.:1032823-75-8
- PTIQ
Catalog No.:BCC7953
CAS No.:1032822-42-6
- GDC-0980 (RG7422)
Catalog No.:BCC4992
CAS No.:1032754-93-0
- GNE-477
Catalog No.:BCC8049
CAS No.:1032754-81-6
- Salidroside
Catalog No.:BCN5966
CAS No.:10338-51-9
- Telotristat
Catalog No.:BCC5128
CAS No.:1033805-28-5
- HPGDS inhibitor 1
Catalog No.:BCC4065
CAS No.:1033836-12-2
- 1-O-Methylnataloe-emodin
Catalog No.:BCN7036
CAS No.:103392-51-4
- Octyl gallate
Catalog No.:BCN8432
CAS No.:1034-01-1
- Disodium (R)-2-Hydroxyglutarate
Catalog No.:BCC6515
CAS No.:103404-90-6
- Devazepide
Catalog No.:BCC7319
CAS No.:103420-77-5
- CTOP
Catalog No.:BCC5780
CAS No.:103429-31-8
- CTAP
Catalog No.:BCC5776
CAS No.:103429-32-9
- Z-Cyclopentyl-AP4
Catalog No.:BCC7616
CAS No.:103439-17-4
- Xanthone V1a
Catalog No.:BCN7922
CAS No.:103450-96-0
- NMS-1286937
Catalog No.:BCC5358
CAS No.:1034616-18-6
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.
