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GNF-5837 Pan-Trk inhibitor

Catalog No.A8303
Size Price Stock Qty
10mM (in 1mL DMSO)
$95.00
In stock
10mg
$103.00
In stock
50mg
$278.00
In stock
200mg
$670.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

GNF-5837

Protocol

Cell experiment [1]:

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.

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.

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Chemical Properties

Cas No. 1033769-28-6 SDF Download 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
Shipping Condition Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
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.

Background

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.