LM11A 31 dihydrochloride
Chemical Name: (2S,3S)-2-Amino-3-methyl-N-[2-(4-morpholinyl)ethyl]pentanamide dihydrochloride
Biological ActivityLM11A 31 dihydrochloride is a nonpeptide p75NTR ligand and nerve growth factor (NGF) antagonist. LM11A 31 blocks p75-mediated cell death, inhibits proNGF induced cell death (IC50 = 1-10 nM), increases proliferation and survival of hippocampal neural progenitors and inhibits Aβ-induced cell death (EC50 = 20 nM). In animal models of Alzheimer's disease LM11A 31 prevents and reverses atrophy of cholinergic neurites and reverses Alzheimer's pathology; in models of Huntington's disease LM11A 31 increases survival, reduces the formation of aggregates of mutant huntingtin and neuronal degeneration. Also promotes functional recovery in a mouse model of spinal cord injury. Orally available and brain penetrant.
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Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death.
Massa et al.
Oral administration of a small molecule targeted to block proNGF binding to p75 promotes myelin sparing and functional recovery after spinal cord injury.
Tep et al.
A small molecule P75NTR ligand protects neurogenesis after traumatic brain injury.
Shi et al.
Stem Cells [Epub ahead of print], 2013;
A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression.
Simmons et al.
PLoS One, 2014;9:e102136
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