2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
生物活性
Description
In Vivo
In Vitro
化合物的使用
Kinase Assay
Cell Assay
Animal Administration
参考文献
Compound 23 was 180-fold selective over TrkB and 70-fold selective over TrkC in cell based
assays (TrkB cell IC50 1.8μM, TrkC cell IC50 0.70μM).Compound 23 exhibited exquisite TrkA selectivity with >95% inhibition of
TrkA and <15% inhibition of all other kinases observed.Compound 23 was shown to inhibit NGF induced phosphorylated ERK formation in native adult
rat DRGs with an IC50 ~57nM and abolished sensitization to capsaicin administration to NGFsensitised
skin as demonstrated by laser Doppler imaging in vivo in anaesthetised rat (see
supporting information, rat non-activated enzyme IC50 6nM).Compound 23 was studied in the UVIH model of inflammatory pain in rats whereby its effect on
thermal hyperalgesia resulting from UV burn was assessed by measuring paw withdrawal latency
(Figure 11). Single oral doses of 23 (1.2, 12 and 40 mg/kg) were administered 48 hours after UV
treatment and paw withdrawal latency determined at 1, 3 and 6 hours post dose. Hyperalgesia was
found to be significantly reversed at doses of 23 of 12 and 40 mg/kg at each of the time-points
studied (p<0.01, 2-way ANOVA vs. vehicle). The positive control ibuprofen (100 mg/kg, p.o.)
also reversed thermal hyperalgesia at the 1 and 3 hour time-points. No effect was seen with any
dose on thermal withdrawal response on the contralateral hindpaw (data not shown).
Determination of unbound plasma concentrations of 23 in animals at 6 hours post dose showed
that statistically significant efficacy was observed at unbound plasma concentrations equivalent to
0.4x (12 mg/kg) and 2.7x (40 mg/kg) TrkA cell IC50 (10nM).
