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Chemical compound
ANA-12
ATC code
N -[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide
CAS Number
PubChem
CID
ChemSpider
UNII
ECHA InfoCard
100.229.925
Formula C 22 H 21 N 3 O 3 S
Molar mass 407.49 g·mol−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 (Kd = 10 nM and 12 μM for the high- and low-affinity sites, respectively), the main
receptor of
brain-derived neurotrophic factor (BDNF).
[1] 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.
[1] It blocks the
neurotrophic actions of BDNF without compromising
neuron survival.
[1]
Research
ANA-12 produces rapid
antidepressant - and
anxiolytic -like effects in
animal models ,
[1] the former of which have been elucidated to be mediated by blockade of BDNF signaling in the
nucleus accumbens .
[2]
[3] 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.
[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] It also blocks hippocampal neurogenesis induced by
physical exercise in rodents, and may block the cognitive-enhancing effects of exercise as well.
[7]
See also
References
^
a
b
c
d 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)