LM22A-4

LM22A-4
Clinical data
ATC code
  • None
Identifiers
  • 1-N,3-N,5-N-tris(2-Hydroxyethyl)benzene-1,3,5-tricarboxamide
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H21N3O6
Molar mass339.348 g·mol−1
3D model (JSmol)
  • C1=C(C=C(C=C1C(=O)NCCO)C(=O)NCCO)C(=O)NCCO
  • 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

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

  1. ^ 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.
  2. ^ a b Lewin G, Carter BD (25 March 2014). Neurotrophic Factors. Springer Science & Business Media. pp. 490–491. ISBN 978-3-642-45106-5.
  3. ^ a b c Annual Reports in Medicinal Chemistry. Elsevier Science. 24 September 2014. pp. 68–. ISBN 978-0-12-800372-5.
  4. ^ Molecular Basis of Memory. Elsevier Science. 30 January 2014. pp. 183–. ISBN 978-0-12-420200-9.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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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