ANA-12 - Misplaced Pages

Chemical compound Pharmaceutical compound

ANA-12
Clinical data

ATC code	None
Identifiers
IUPAC name N-phenyl]-1-benzothiophene-2-carboxamide
CAS Number	219766-25-3
PubChem CID	2799722
ChemSpider	2078460
UNII	54S4JPT8JX
CompTox Dashboard (EPA)	DTXSID501045818
ECHA InfoCard	100.229.925
Chemical and physical data
Formula	C₂₂H₂₁N₃O₃S
Molar mass	407.49 g·mol
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, the main receptor of brain-derived neurotrophic factor (BDNF). ANA-12 was originally discovered and developed by Cazorla M. and colleagues at Université Paris and Inserm in 2011. 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 has two binding sites on TrkB, a high- and low-affinity site (K_d = 10 nM and 12 μM, respectively).

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.

References

^ 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.

Growth factor receptor modulators

Angiopoietin

Agonists: Angiopoietin 1
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Antagonists: Angiopoietin 2
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Kinase inhibitors: Altiratinib
CE-245677
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CNTF

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CNTF
Dapiclermin

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors: Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF

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LNGF (p75)

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ASP-6294
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PDGF

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Platelet-derived growth factor (A, B, C, D)

RET (GFL)

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib
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GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib
GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib
Unsorted	Kinase inhibitors: Agerafenib