5.04981

Tie2/Trk Dual Inhibitor

• Synonym(s): Tie2/Trk Dual Inhibitor, Tie2 Inhibitor IV, Trk Inhibitor VII
• Empirical Formula (Hill Notation): C₂₃H₂₁ClN₆O₂
• CAS Number: 717899-32-6
• Molecular Weight: 448.90
• UNSPSC Code: 12352200

Properties

• assay: ≥99% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 50 mg/mL
• storage temp.: 2-8°C

Description

General description

A cell-permeable pyrrolopyrimidinyl-phenyl urea that acts as a potent, reversible, ATP-competitive inhibitor against Tie2 and TrkA kinase activity in cell-free assays (IC₅₀ = 40 and 0.4 nM, respectively; [ATP] = 100 µM) as well as Tie2- and TrkA-dependent tyrosine phosphorylation of cellular proteins upon ligand stimulation in cultures (IC₅₀ = 3.7 and 4 nM, respectively, using respective NIH 3T3 transfectant; 1 h drug preincubation), displaying much reduced potency against PDGFR (IC₅₀ =1.4 µM) and little or no inhibitory activity toward EGFR, FGFR, or KDR (IC₅₀ >10 µM). Reported to be orally available in rat (systemic C_max = 1,715 ng/mL; T_max = 0.75 h; 4.2 mg/kg p.o. using ultrafasted rats) and efficacious in suppressing rat C6 glioblastoma tumor expansion (by 40%, 60%, and 70% in 10 d, respectively, with 10 mg/kg/d, 33 mg/kg/d, or 10 mg/kg/12 h oral dosing schedule) in vivo.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
TrkA

Reversible: yes

Secondary Target
Tie-2

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

Arcari, J.T., et al. 2013. Bioorg. Med. Chem. Lett.23, 3059.

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