219766-25-3

Basic information

• Product Name: ANA12
• 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
• CAS NO: 219766-25-3
• Molecular Formula: C22H21N3O3S
• Molecular Weight: 407.48544
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 219766-25-3.mol
• Article Data: 0

Chemical Properties

• Appearance: white to beige/
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥5mg/mL at 60°C
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• CAS DataBase Reference: ANA12(CAS DataBase Reference)
• NIST Chemistry Reference: ANA12(219766-25-3)
• EPA Substance Registry System: ANA12(219766-25-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 219766-25-3(Hazardous Substances Data)

Usage

Description

ANA-12, also known as 219755-25-3, is a TrkB receptor antagonist that selectively binds to two distinct receptor sites, preventing activation by BDNF in a non-competitive manner. It exhibits a high affinity for the high affinity site with a Kd of 10 nM and a Kd of 12 μM for the low affinity site. Systemic administration of ANA-12 in adult mice has been shown to decrease TrkB activity in the brain without affecting neuronal survival or altering TrkA and TrkC functions. ANA-12 has demonstrated antidepressant and anxiolytic properties in mouse models, as well as potential benefits in the treatment of LPS-induced depression-like behavior and cognitive decline during calorie restriction.

Uses

Used in Pharmaceutical Industry:
ANA-12 is used as a selective TrkB antagonist for inhibiting TrkB in primary mouse cortical neurons and primary rat hippocampal cultures. This application is crucial for understanding the role of BDNF in various neurological processes and the development of new neurotrophic agents.
Used in Antidepressant Applications:
ANA-12 is used as an antidepressant agent for demonstrating antidepressant effects on LPS-induced depression-like behavior in mice. Its ability to modulate TrkB activity makes it a promising candidate for the development of novel treatments for depression and related mood disorders.
Used in Anxiety Treatment:
ANA-12 is used as an anxiolytic agent for exhibiting anxiolytic properties in mouse models after systemic administration. This suggests its potential utility in the development of new treatments for anxiety disorders.
Used in Cognitive Decline Research:
ANA-12 is used as a research tool for elucidating the role of BDNF in the improvement of cognitive decline during calorie restriction. This application aids in understanding the underlying mechanisms of cognitive decline and the potential therapeutic benefits of ANA-12 in this context.
Used in Neurotrophic Agent Discovery:
ANA-12 is used as a research tool in the discovery of new neurotrophic agents. Its ability to selectively target TrkB receptors and modulate BDNF signaling pathways makes it a valuable asset in the development of novel therapeutic strategies for various neurological conditions.

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.

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.

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