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Overview
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Background
ANA 12 is a potent and selective antagonist of TrkB with IC50 values of 45.6 nM and 41.1 μM for the high and low affinity sites, respectively [1].
Tropomyosin-related kinase B (TrkB) is a receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and activates 3 major signaling pathways involving phospholipase C-γ, PI3K and MAPK. The BDNF/TrkB signaling plays an important role in drug addiction, depression and anxiety [1].
ANA 12 is a potent and selective TrkB antagonist. ANA-12 bound to the extracellular low-affinity site of TrkB with Kd value of 12 μM in a dose-dependent way. And ANA-12 bound to the high-affinity site with Kd value of 10 nM. Also, ANA-12 bound to TrkB in a noncompetitive mechanism. In the TrkB-expressing cells, ANA-12 (10 nM) effectively inhibited BDNF-induced neurite outgrowth and completely abolished the effects of BDNF at 10-100 μM [1].
In the mice brain, ANA-12 (0.5 mg/kg) inhibited endogenous TrkB activity by 25% 4 hours later. Also, ANA-12 showed antidepressant and anxiolytic activities [1].
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