GNF-5837

Names

[ Name ]:
GNF-5837

[Synonym ]:
Urea, N-[3-[[(3Z)-2,3-dihydro-2-oxo-3-(1H-pyrrol-2-ylmethylene)-1H-indol-6-yl]amino]-4-methylphenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]-
1-[2-Fluoro-5-(trifluoromethyl)phenyl]-3-(4-methyl-3-{[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-6-yl]amino}phenyl)urea
GNF5837

Biological Activity

[Description]:

GNF-5837 is a potent pan-Trk inhibitor which display 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).IC50 Value: 7/9/11 nM (Tel-TrkC/Tel-TrkB/Tel-TrkA) [1]Target: pan-TrkGNF-5837 is an orally bioavailable oxindole compound that and acts as a potent, reversible and type II DFG-out inhibitor of pan-Trk activity (IC50 = 8 and 12 nM for TrkA and TrkB). Shown to target Trk (tropomyosin receptor kinase) ATP binding cleft and an immediately adjacent hydrophobic pocket. Preferentially arrests the proliferation of Ba/F3 cells fused with Tel-TrkA, Tel-TrkB and Tel-TrkC (IC50 = 11, 9 and 7 nM, respectively) and in Ba/F3 and RIE cells expressing both TrkA and NGF (IC50 = 42 and 17 nM, respectively) over Mo7e-c-Kit and Rat-A10-PDGFR (IC50 = 1 and 0.5 μM) and Ba/F3-Tel-KDR and wt-Ba/F3 cells (IC50 = 3.0 and 5.6 μM). GNF-5837 displays ~100-fold greater selectivity among a panel of 59 closely related kinases and in 33 cellular kinase assays. GNF-5837 weakly antagonize relevant cytochrome P450 isozymes and hERG channel, and exhibit adequate microsomal stability, pharmacokinetic profile and efficacy in mice and rats. GNF-5837 suppresses tumor growth in a mouse RIE-TrkAmNGF xenograft model (50 mg/kg, p.o.) [1].

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Trk Receptor

Research Areas >> Cancer

[References]

[1]. Albaugh, P. et al. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS MEDICINAL CHEMISTRY LETTERS, 2012; 3 (2): 140

[Related Small Molecules]

Entrectinib | LOXO-101 | ANA-12 | LM22B 10 | GW441756 | Repotrectinib | Altiratinib | LM22A-4 | Selitrectinib (LOXO-195) | Tyrphostin AG 879 | Belizatinib | Tavilermide | AZ-23 | CH7057288 | CE-245677

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
616.0±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₈H₂₁F₄N₅O₂

[ Molecular Weight ]:
535.492

[ Flash Point ]:
326.4±31.5 °C

[ Exact Mass ]:
535.163147

[ PSA ]:
98.05000

[ LogP ]:
6.33

[ Appearance of Characters ]:
yellow to orange

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.714

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: soluble5mg/mL, clear (warmed)

Safety Information

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
36/37/39

[ RIDADR ]:
NONH for all modes of transport

Related Compounds

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