Tie2/Trk Dual Inhibitor

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.

Cell permeable: yes

Primary Target
TrkA

Reversible: yes

Secondary Target
Tie-2

Packaged under inert gas

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

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

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

Toxicity: Standard Handling (A)