From Wikipedia, the free encyclopedia
Chemical compound
LM22A-4
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ATC code | |
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1-N,3-N,5-N-tris(2-Hydroxyethyl)benzene-1,3,5-tricarboxamide
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CAS Number | |
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PubChem
CID | |
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ChemSpider | |
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CompTox Dashboard (
EPA) | |
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Formula | C15H21N3O6 |
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Molar mass | 339.348 g·mol−1 |
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3D model (
JSmol) | |
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C1=C(C=C(C=C1C(=O)NCCO)C(=O)NCCO)C(=O)NCCO
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InChI=1S/C15H21N3O6/c19-4-1-16-13(22)10-7-11(14(23)17-2-5-20)9-12(8-10)15(24)18-3-6-21/h7-9,19-21H,1-6H2,(H,16,22)(H,17,23)(H,18,24) Key:RGWJKANXFYJKHN-UHFFFAOYSA-N
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LM22A-4 is a
synthetic,
selective
small-molecule
partial agonist of
TrkB (
EC50 for TrkB activation = 200–500 pM;
IC50 for inhibition of BDNF binding to TrkB = 47 nM;
IA = ~85%), the main
receptor of
brain-derived neurotrophic factor.
[1]
[2]
[3] It has been found to possess poor
blood-brain-barrier penetration when administered systemically, so LM22A-4 has been given to animals instead via
intranasal administration, with
central nervous system TrkB activation observed.
[3]
[4] The compound produces
neurogenic and
neuroprotective effects in animals,
[3]
[5]
[6] and shows beneficial effects on
respiration in
animal models of
Rett syndrome.
[2][
citation needed]
[7]
See also
References
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^ Massa SM, Yang T, Xie Y, Shi J, Bilgen M, Joyce JN, et al. (May 2010).
"Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents". The Journal of Clinical Investigation. 120 (5): 1774–85.
doi:
10.1172/JCI41356.
PMC
2860903.
PMID
20407211.
- ^
a
b Lewin G, Carter BD (25 March 2014).
Neurotrophic Factors. Springer Science & Business Media. pp. 490–491.
ISBN
978-3-642-45106-5.
- ^
a
b
c
Annual Reports in Medicinal Chemistry. Elsevier Science. 24 September 2014. pp. 68–.
ISBN
978-0-12-800372-5.
-
^
Molecular Basis of Memory. Elsevier Science. 30 January 2014. pp. 183–.
ISBN
978-0-12-420200-9.
-
^ Wegrzyn RD, Rudolph AS (26 April 2012).
Alzheimer's Disease: Targets for New Clinical Diagnostic and Therapeutic Strategies. CRC Press. pp. 189–.
ISBN
978-1-4398-2708-6.
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^ Numakawa T (August 2014).
"Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases". Neural Regeneration Research. 9 (16): 1506–8.
doi:
10.4103/1673-5374.139474.
PMC
4192965.
PMID
25317165.
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^ Pietropaolo S, Sluyter F,
Crusio WE (25 September 2014).
Behavioral Genetics of the Mouse: Volume 2, Genetic Mouse Models of Neurobehavioral Disorders. Cambridge University Press. pp. 139–.
ISBN
978-1-316-06140-4.
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Angiopoietin | |
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CNTF | |
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EGF (ErbB) | |
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FGF |
FGFR1 | |
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FGFR2 |
- Agonists:
Ersofermin
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FGF (
1,
2 (bFGF),
3,
4,
5,
6,
7 (
KGF),
8,
9,
10 (KGF2),
17,
18,
22)
-
Palifermin
-
Repifermin
-
Selpercatinib
-
Sprifermin
-
Trafermin
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FGFR3 | |
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FGFR4 | |
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Unsorted | |
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HGF (c-Met) | |
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IGF | |
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LNGF (p75NTR) | |
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PDGF | |
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RET (GFL) | |
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SCF (c-Kit) | |
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TGFβ | |
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Trk |
TrkA |
- Negative allosteric modulators:
VM-902A
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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
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N-Acetylserotonin
-
NT-3
-
NT-4
-
Norwogonin (5,7,8-THF)
-
R7
-
R13
-
TDP6
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TrkC | |
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VEGF | |
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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)
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Erythropoietin (see
here instead)
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Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF)
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Glia maturation factor (GMF)
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Hepatoma-derived growth factor (HDGF)
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Interleukins/
T-cell growth factors (see
here instead)
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Leukemia inhibitory factor (LIF)
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Macrophage-stimulating protein (MSP; HLP, HGFLP)
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Midkine (NEGF2)
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Migration-stimulating factor (MSF; PRG4)
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Oncomodulin
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Pituitary adenylate cyclase-activating peptide (PACAP)
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Pleiotrophin
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Renalase
-
Thrombopoietin (see
here instead)
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Wnt signaling proteins
- Additional growth factor receptor modulators:
Cerebrolysin (neurotrophin mixture)
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