Overview
- Wood, E.R. et al. (2004) Bioorg. Med. Chem. Lett. 14, 953.
Alomone Labs GW441756 hydrochloride inhibits NGF-induced survival of PC12 cells.PC12 cells were incubated for 24 hours with or without 2 nM Native mouse NGF 2.5S protein (>95%) (#N-100), inducing 5 fold increase in cell numbers measured with XTT. Increasing concentrations of GW441756 hydrochloride (#G-191), induced dose dependent inhibition of the NGF effect with apparent IC50 of about 2 µM.
GW441756 is a potent and selective inhibitor of the NGF receptor tyrosine kinase A (TrkA). This compound also inhibits TrkB and TrkC but displays significantly higher selectivity for TrkA receptor than other TrkA inhibitors and a 100-fold selectivity over a range of other kinases. The IC50 value of GW441756 is 2 nM1,3.
The compound induces a dose-dependent decrease in neoplastic proliferation and has the ability to increase levels of caspase-3 that can lead to apoptosis.
Previous studies have shown that TrKA inhibitors have a relevant anti-proliferative effects in neoplasia compare to other TrkA inhibitors with a lower effective dosage1,3.
Signaling through protein tyrosine kinase receptors is important for neuronal metabolism, promotion of neuronal survival, stimulating neurite growth, synaptogenesis and potentiating synaptic strength2.
