Tablets, 100 mg TID, 14 days

Primary pharmacological activity was assessed using stably transfected U2OS cells expressing human TrkA, TrkB or TrkC (DiscoverX PathHunter system) in the presence of p75. 4 mM stock solutions of test compounds (PF-06273340) are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135, WO2005/116035 at a maximum concentration of 150 μM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 μM of the compound of Example 135, WO2005/116035 and 0% effect (ZPE) is defined by 100% DMSO. Plates containing 1 ul of serially diluted compound, standard and HPE/ZPE were diluted 1/66 in assay buffer (PBS minus Ca2+, minus Mg2+ with 0.05% pluronic F127) using a Wellmate. Using a Platemate Plus, 5 μl of 1/66 diluted test compounds were then transferred to the cell plate and allowed to reach equilibrium by incubating for 30 min at room temperature before addition of agonist stimulus: 10 μl/well of 2nM (0.571nM FAC) of the cognate neurotrophin (Peprotech) diluted in agonist buffer (HBSS with 0.25% BSA). Final assay concentration of the test compounds was 8.66 M. The plates were left at room temperature for a further 2 hours before addition of 10 μl of the DiscoveRx PathHunter detection reagent. After reagent addition, plates were covered and incubated at room temperature for 60 minutes. Luminescence signal was read using an Envision plate reader. Test compound data were expressed as percentage inhibition defined by HPE and ZPE values for each plate.