ANA-12 (219755-25-3) is a TrkB receptor antagonist. Binds to two distinct receptor sites preventing activation by BDNF non-competitively, IC50 = 45.6 nM and 41.1 μM for the high and low affinity sites respectively. Systemic administration to adult mice decreased TrkB activity in the brain without affecting neuronal survival or altering TrkA and TrkC functions. ANA-12 displays antidepressant and anxiolytic properties in mouse models after systemic administration.1 Shows antidepressant effects on LPS-induced depression-like behavior in mice.2 ANA-12 has been used to elucidate the role of BDNF in improvement of cognitive decline during calorie restriction3 and in the discovery of new neurotrophic agents4.
1) Cazorla et al. (2011), Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice; J. Clin. Invest., 121 1846
2) Zhang et al. (2014), Antidepressant effects of TRKB ligands on depression-like behavior and dendritic changes in mice after inflammation; J. Neuropsychopharmacol., 18 pyu077
3) Kishi et al. (2015), Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus of obesity-induced hypertensive rats; Int. Heart J., 56 110
4) Chakravarty et al. (2015) A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action; Sci. Rep., 5 14134