ANA-12

ANA-12

Systematic (IUPAC) name
N-[2-[(2-Oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide
Identifiers
CAS Number	219766-25-3
ATC code	None
PubChem	CID: 2799722
ChemSpider	2078460
Chemical data
Formula	C22H21N3O3S
Molecular mass	407.48544 g/mol
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 highly potent, 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.

ANA-12 produces rapid antidepressant- and anxiolytic-like effects in animal models of depression and anxiety, respectively, 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

• Cyclotraxin B
• K252a
• LM22A-4
• Deoxygedunin
• HIOC
• N-Acetylserotonin