ANA-12

ANA-12

Clinical data
ATC code	None
Identifiers
IUPAC name N-[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide
CAS Number	219766-25-3 Y
PubChem CID	2799722
ChemSpider	2078460
UNII	54S4JPT8JX
ECHA InfoCard	100.229.925
Chemical and physical data
Formula	C22H21N3O3S
Molar mass	407.49 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CCNC(=O)C(C1)NC(=O)C2=CC=CC=C2NC(=O)C3=CC4=CC=CC=C4S3
InChI InChI=1S/C22H21N3O3S/c26-20(25-17-10-5-6-12-23-21(17)27)15-8-2-3-9-16(15)24-22(28)19-13-14-7-1-4-11-18(14)29-19/h1-4,7-9,11,13,17H,5-6,10,12H2,(H,23,27)(H,24,28)(H,25,26) Key:TUSCYCAIGRVBMD-UHFFFAOYSA-N

ANA-12 is a selective, small-molecule non-competitive antagonist of TrkB (K_d = 10 nM and 12 μM for the high- and low-affinity sites, respectively), the main receptor of brain-derived neurotrophic factor (BDNF). The compound crosses the blood-brain-barrier and exerts central TrkB blockade, producing effects as early as 30 minutes (~400 nM) and as long as 6 hours (~10 nM) following intraperitoneal injection in mice. It blocks the neurotrophic actions of BDNF without compromising neuron survival.

Research

ANA-12 produces rapid antidepressant- and anxiolytic-like effects in animal models, the former of which have been elucidated to be mediated by blockade of BDNF signaling in the nucleus accumbens. It has also been found to alleviate methamphetamine-induced depression-like behavior (including anhedonia), behavioral sensitization, and nucleus accumbens neuroplasticity changes with subchronic (14-day) administration in mice, whereas the TrkB agonist 7,8-dihydroxyflavone was ineffective in doing so.

ANA-12 blocks the cognitive-enhancing effects of environmental enrichment and calorie restriction in rodents, which are mediated by BDNF signaling through TrkB in the hippocampus. It also blocks hippocampal neurogenesis induced by physical exercise in rodents, and may block the cognitive-enhancing effects of exercise as well.

See also

• Tropomyosin receptor kinase B § Antagonists