Biochem/physiol Actions

Reversible: yes

Secondary TargetTie-2

Primary TargetTrkA

Cell permeable: yes

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, with respective NIH 3T3 transfectant), 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 efficacious in suppressing rat C6 glioblastoma tumor expansion (10 to 33 mg/kg/d, or 10 mg/kg/12 h p.o.) in vivo.

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.

Legal Information

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

Other Notes

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

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

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

Warning

Toxicity: Standard Handling (A)