Chemical compound
Pharmaceutical compound
ANA-12 ATC code
N -[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide
CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA ) ECHA InfoCard 100.229.925 Formula C 22 H 21 N 3 O 3 S Molar mass −1 3D model (JSmol )
C1CCNC(=O)C(C1)NC(=O)C2=CC=CC=C2NC(=O)C3=CC4=CC=CC=C4S3
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 , the main receptor of brain-derived neurotrophic factor (BDNF).[ 1] Université Paris and Inserm in 2011.[ 1] 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.[ 1] neurotrophic actions of BDNF without compromising neuron survival.[ 1]
Research
ANA-12 has two binding sites on TrkB, a high- and low-affinity site (Kd = 10 nM and 12 μM, respectively).
ANA-12 produces rapid antidepressant - and anxiolytic -like effects in animal models ,[ 1] nucleus accumbens .[ 2] [ 3] 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.[ 4]
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 .[ 5] [ 6] physical exercise in rodents, and may block the cognitive-enhancing effects of exercise as well.[ 7]
See also
References
^ a b c d e Cazorla M, Prémont J, Mann A, Girard N, Kellendonk C, Rognan D (May 2011). "Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice" . The Journal of Clinical Investigation . 121 (5): 1846– 1857. doi :10.1172/JCI43992 . PMC 3083767 PMID 21505263 . ^ Zhang JC, Wu J, Fujita Y, Yao W, Ren Q, Yang C, et al. (October 2014). "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation" . The International Journal of Neuropsychopharmacology . 18 (4): pyu077. doi :10.1093/ijnp/pyu077 . PMC 4360225 PMID 25628381 . ^ Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K (December 2015). "Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist". European Neuropsychopharmacology . 25 (12): 2449– 2458. doi :10.1016/j.euroneuro.2015.09.002 . PMID 26419294 . S2CID 851 . ^ Ren Q, Ma M, Yang C, Zhang JC, Yao W, Hashimoto K (October 2015). "BDNF-TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms" . Translational Psychiatry . 5 (10): e666. doi :10.1038/tp.2015.157 . PMC 4930133 PMID 26506052 . ^ Fan D, Li J, Zheng B, Hua L, Zuo Z (January 2016). "Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression". Molecular Neurobiology . 53 (1): 344– 354. doi :10.1007/s12035-014-9013-1 . PMID 25432890 . S2CID 15795328 . ^ Kishi T, Hirooka Y, Nagayama T, Isegawa K, Katsuki M, Takesue K, Sunagawa K (2015). "Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats" . International Heart Journal . 56 (1): 110– 115. doi :10.1536/ihj.14-168 PMID 25503654 . ^ Ambrogini P, Lattanzi D, Ciuffoli S, Betti M, Fanelli M, Cuppini R (October 2013). "Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF". Brain Research . 1534 : 1– 12. doi :10.1016/j.brainres.2013.08.023 . hdl :11576/2575580 . PMID 23973748 . S2CID 35405574 .
Angiopoietin CNTF EGF (ErbB)
FGF
FGFR1 FGFR2
Agonists: Ersofermin FGF (1 , 2 (bFGF) , 3 , 4 , 5 , 6 , 7 (KGF ), 8 , 9 , 10 (KGF2) , 17 , 18 , 22 )Palifermin Repifermin Selpercatinib Sprifermin Trafermin FGFR3 FGFR4 Unsorted
HGF (c-Met) IGF
LNGF (p75NTR ) PDGF RET (GFL)
SCF (c-Kit) TGFβ Trk
TrkA
Negative allosteric modulators: VM-902A TrkB
Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 TrkC
VEGF Others
Additional growth factors: Adrenomedullin Colony-stimulating factors (see here instead)Connective tissue growth factor (CTGF) Ephrins (A1 , A2 , A3 , A4 , A5 , B1 , B2 , B3 )Erythropoietin (see here instead)Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins /T-cell growth factors (see here instead)Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (see here instead)Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
Information related to ANA-12
