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.

• Synonyme(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
• Formule empirique (notation de Hill): C₂₈H₂₁F₄N₅O₂
• Numéro CAS: 1033769-28-6
• Poids moléculaire : 535.49
• Numéro MDL: MFCD24386809
• Code UNSPSC : 12352200

Propriétés

• Niveau de qualité: 100
• Pureté: ≥98% (HPLC)
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: orange
• Solubilité: DMSO: 50 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: 2-8°C
• Chaîne SMILES: 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-
• Clé InChI: YYDUWLSETXNJJT-MTJSOVHGSA-N

Description

Description générale

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.).

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

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

Autres remarques

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

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable