648451

Trk Inhibitor III, GNF-5837

The Trk Inhibitor III, GNF-5837 controls the biological activity of Trk. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.

• Synonym(s): Trk Inhibitor III, GNF-5837, (Z)-1-(3-((3-((1H-Pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)-4-methylphenyl)-3-(2-fluoro-5-(trifluoromethyl)phenyl)urea
• Empirical Formula (Hill Notation): C₂₈H₂₁F₄N₅O₂
• CAS Number: 1033769-28-6
• Molecular Weight: 535.49
• MDL number: MFCD24386809
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• assay: ≥98% (HPLC)
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: orange
• solubility: DMSO: 50 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: O=C(NC1=C(C=CC(C(F)(F)F)=C1)F)NC2=CC(NC3=CC(NC/4=O)=C(C=C3)C4=C\C5=CC=CN5)=C(C)C=C2
• 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-
• InChI key: YYDUWLSETXNJJT-MTJSOVHGSA-N

Description

General description

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). Displays ~100-fold greater selectivity among a panel of 59 closely related kinases and in 33 cellular kinase assays. Weakly active against relevant cytochrome P450 isozymes and hERG channel, and exhibit adequate microsomal stability, pharmacokinetic profile and efficacy in mice and rats. Suppresses tumor growth in a mouse RIE-TrkAmNGF xenograft model (50 mg/kg, p.o.).

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Albaugh, P., et al. 2012. ACS Med. Chem. Lett.3, In press.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable