LM22A-4

LM22A-4
Clinical data

ATC code	None
Identifiers
IUPAC name 1-N,3-N,5-N-tris(2-Hydroxyethyl)benzene-1,3,5-tricarboxamide
CAS Number	37988-18-4
PubChem (CID)	2054170
ChemSpider	1548402
Chemical and physical data
Formula	C₁₅H₂₁N₃O₆
Molar mass	339.34374 g/mol
3D model (Jmol)	Interactive image
SMILES C1=C(C=C(C=C1C(=O)NCCO)C(=O)NCCO)C(=O)NCCO
InChI 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]^[7]

References

↑ 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.
1 2 Gary Lewin; Bruce D. Carter (25 March 2014). Neurotrophic Factors. Springer Science & Business Media. pp. 490–491. ISBN 978-3-642-45106-5.
1 2 3 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.
↑ 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.
↑ 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.
↑ 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.

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) Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab Kinase inhibitors: Afatinib AG-490 Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154

ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib AG-490 Lapatinib Mubritinib Neratinib

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))

FGFR1	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Trafermin Velafermin

FGFR2	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin

FGFR3	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Sprifermin Trafermin Antibodies: Burosumab (against FGF23)

FGFR4	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin

Unsorted	Agonists: FGF15/19

IGF-1	Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Antagonists: BMS-754807 Antibodies: AVE1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Kinase inhibitors: Linsitinib NVP-ADW742 NVP-AEW541 OSl-906

IGF-2	Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab

Others	Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib

GFRα2	Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib

GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib

GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib

Unsorted	Kinase inhibitors: Agerafenib

TrkA	Agonists: Amitriptyline Cenegermin Gambogic amide NGF Tavilermide Antagonists: FX007 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101 Antibodies: Against NGF: Fasinumab Fulranumab Ranevetmab Tanezumab

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 Deoxygedunin Diosmetin HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

TrkC	Agonists: NT-3 Kinase inhibitors: Entrectinib K252a Lestaurtinib LOXO-101

Others

Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)

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