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LM22A-4 structure.svg
Clinical data
ATC code
  • None
CAS Number
PubChem CID
Chemical and physical data
Molar mass339.344 g/mol g·mol−1
3D model (JSmol)

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


  1. ^ Massa, Stephen M.; Yang, Tao; Xie, Youmei; Shi, Jian; Bilgen, Mehmet; Joyce, Jeffrey N.; Nehama, Dean; Rajadas, Jayakumar; Longo, Frank M. (2010). "Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents". Journal of Clinical Investigation. 120 (5): 1774–1785. doi:10.1172/JCI41356. ISSN 0021-9738. PMC 2860903. PMID 20407211.
  2. ^ a b Gary Lewin; Bruce D. Carter (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. ^ Renee D. Wegrzyn; Alan S. Rudolph (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, Tadahiro (2014). "Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases". Neural Regeneration Research. 9 (16): 1506. doi:10.4103/1673-5374.139474. ISSN 1673-5374. PMC 4192965.
  7. ^ Susanna Pietropaolo; Frans Sluyter; Wim E. Crusio (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.