GNF-5837 |
| Catalog No.GC16343 |
Pan-Trk inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1033769-28-6
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
Ba/F3 and RIE cells expressing both TRKA and NGF |
|
Preparation method |
The solubility of this compound in DMSO is > 17 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.17 nM ~ 10 uM; 48 hrs |
|
Applications |
In Ba/F3 cells expressing TRKA and NGF, GNF-5837 displayed potent antiproliferation activity, with an IC50 value of 0.042 μM. However, in parental Ba/F3 cells whose proliferation is IL-3-driven, GNF-5837 did not show antiproliferative activity up to 10 μM. On the other hand, GNF-5837 could also significantly inhibited cell growth and proliferation of RIE cells expressing TRKA and NGF, with an IC50 value of 0.017 μM. |
| Animal experiment [1]: | |
|
Animal models |
Rie-TRKAmNGF xenografted mouse model |
|
Dosage form |
25, 50 or 100 mg/kg; p.o.; q.d., for 10 days |
|
Applications |
After the 10-day treatment, 72% and 100% tumor regression were observed at the 50 mg/kg and 100 mg/kg treatment groups, respectively. At the dose of 25 mg/kg, GNF-5837 only partially inhibited tumor growth in Rie-TRKAmNGF xenografted mouse model. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Albaugh P, 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. | |
| Cas No. | 1033769-28-6 | SDF | |
| Chemical Name | (Z)-1-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)-4-methylphenyl)-3-(2-fluoro-5-(trifluoromethyl)phenyl)urea | ||
| Canonical SMILES | O=C(NC1=CC(C(F)(F)F)=CC=C1F)NC2=CC=C(C)C(NC3=CC(NC/4=O)=C(C=C3)C4=C\C5=CC=CN5)=C2 | ||
| Formula | C28H21F4N5O2 | M.Wt | 535.49 |
| Solubility | ≥ 17mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8674 mL | 9.3372 mL | 18.6745 mL |
| 5 mM | 0.3735 mL | 1.8674 mL | 3.7349 mL |
| 10 mM | 0.1867 mL | 0.9337 mL | 1.8674 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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