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LM22A-4 is a brain-derived neurotrophic factor (BDNF) mimetic and agonist of the receptor tropomyosin-related kinase B (TrkB, IC50 = 47 nM in a fluorescence anisotropy assay). It selectively inhibits BDNF binding to 3T3 cells expressing TrkB over those expressing TrkA, TrkC, or p75NTR. In vitro, LM22A-4 increases survival of hippocampal neurons via activation of TrkB as well as Akt and ERK downstream pro-survival signaling pathways. In vivo, LM22A-4 increases dwell time in an accelerating rotarod task, indicating improved motor learning in a rat model of traumatic brain injury. LM22A-4 restores TrkB phosphorylation in the medulla and pons and breathing frequency to wild-type levels in a mouse model of Rett syndrome when administered at a dose of 50 mg/kg. It reduces neurite degeneration, formation of intranuclear huntingtin aggregates, and improves downward climbing and grip strength in mouse models of Huntington's disease. LM22A-4 (0.22 mg/kg) also improves limb swing speed and accelerates return to normal gait accuracy in a mouse model of hypoxic-ischemic stroke.Formal Name: N1,N3,N5-tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide. CAS Number: 37988-18-4. Molecular Formula: C15H21N3O6. Formula Weight: 339.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 30 mg/ml, PBS (pH 7.2): 10 mg/ml. SMILES: O=C(NCCO)C1=CC(C(NCCO)=O)=CC(C(NCCO)=O)=C1. InChi Code: 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). InChi Key: RGWJKANXFYJKHN-UHFFFAOYSA-N.
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