| Identification | Back Directory | [Name]
ANA12 | [CAS]
219766-25-3 | [Synonyms]
ANA12
N-(2-((2-oxoazepan-3-yl)carbamoyl)phenyl)benzo[b]thiophene-2-carboxamide
N-[2-[[(Hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide | [EINECS(EC#)]
803-090-7 | [Molecular Formula]
C22H21N3O3S | [MDL Number]
MFCD00117444 | [MOL File]
219766-25-3.mol | [Molecular Weight]
407.49 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMSO: ≥5mg/mL at 60°C | [form ]
powder | [color ]
white to beige | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months. |
| Questions And Answer | Back Directory | [Description]
ANA-12 is a selective TrkB antagonist with Kd of 10 nM and 12 μM for the high and low affinity sites, respectively. | [In vitro]
ANA-12 binds directly and selectively to TrkB and inhibits processes downstream of TrkB without altering TrkA and TrkC functions. In nnr5 PC12-TrkB cells, ANA-12 prevents brain-derived neurotrophic factor (BDNF)-induced neurite outgrowth at concentrations as low as 10 nM. In DRG neurons, ANA-12 eliminates the effect of BDNF on increasing inward current. | [In vivo]
In adult C57BL6/129SveV F1s mice, ANA-12 (0.5 mg/kg, i.p.) decreases TrKB activity in the brain and reduces the anxiety- and depression-related behaviors without affecting the neuron survival. In male C57BL/6 mice, ANA-12 (0.5 mg/kg, i.p.) shows antidepressant-like effects on lipopolysaccharide-induced depression-like behavior. In male Sprague-Dawley rats, ANA-12 (3 μg/dose) blocks the effect of medial nucleus tractus solitarius (mNTS) BDNF on reducing food intake. In male wild-type mice, ANA-12 reverses ethanol intake and induces D3 receptor downregulation, but is ineffective in D3R-/- mice. In male CocSired rats, ANA-12 (0.5 mg/kg, i.p.) reverses the diminished self-administration of cocaine. |
| Hazard Information | Back Directory | [Uses]
ANA-12 was used to inhibit TrkB in primary mouse cortical neurons and primary rat hippocampal cultures. | [Definition]
ChEBI: ANA-12 is a secondary carboxamide that is anthranilic acid in which the carboxy group has undergone condensation with the primary amino group of alpha-amino-epsilon-caprolactam, while the aryl-amino group has undergone condensation with the carboxy group of 1-benzothiophene-2-carboxylic acid. It is a selective, non-competitive antagonist of tropomyosin receptor kinase B (TrkB, also known as tyrosine receptor kinase B). It has a role as a tropomyosin-related kinase B receptor antagonist, an antidepressant and an anxiolytic drug. It is a secondary carboxamide, a member of caprolactams and a member of 1-benzothiophenes. It is functionally related to a 2-aminohexano-6-lactam and an anthranilic acid. | [Biochem/physiol Actions]
The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) have emerged as key mediators in the pathophysiology of several mood disorders, including anxiety and depression. ANA-12 is a TrkB ligand that prevents activation of the receptor by BDNF with a high potency. It binds selectively to TrkB and inhibits processes downstream of TrkB without altering TrkA and TrkC functions. In adult mice model ANA-12 decreases TrkB activity in the brain without affecting neuronal survival. Mice dosed with ANA-12 show reduced anxiety- and depression related behaviors on a variety of tests predictive of anxiolytic and antidepressant properties in humans. ANA-12 may be a valuable tool for studying BDNF/TrkB signaling and may constitute a lead compound for developing the next generation of therapeutic agents for the treatment of mood disorders. There is also N-T19, which is less potent. | [storage]
Store at +4°C | [References]
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 |
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