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LM11A-31 is a p75 neurotrophin receptor (p75NTR) ligand that inhibits nerve growth factor (NGF) binding to p75NTR-Fc (A2 = 1,192 nM).1 It inhibits DNA damage in and promotes survival of hippocampal neuronal cultures in a p75NTR- and concentration-dependent manner. LMA11A-31 also inhibits proNGF-induced cell death of mature oligodendrocytes. In vivo, LMA11A-31 (10-100 mg/kg) improves motor function and coordination in the weight-bearing open-field test and nonweight-bearing swim test and increases survival of oligodendrocytes in a mouse model of spinal contusion injury.2 It prevents and/or reverses atrophy of forebrain cholinergic neurites and cortical dystrophic neurites in Thy-1 hAPPLond/Swe and Tg2576 mice with mid- to late stage Alzheimer's disease.3 It also reduces excessive alcohol self-administration in rats and decreases huntingtin (Htt) aggregate formation and striatal cholinergic degeneration in the R6/2 mouse model of Huntington's disease.4,5
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1. Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-
2. Oral administration of a small molecule targeted to block proNGF binding to p75 promotes myelin sparing and functional recovery after spinal cord injury. J. Neurosci. 33(2), 397-410 (2013).
3. A small molecule p75NTR ligand, LM11A-
4. The neurotrophic factor receptor p75 in the rat dorsolateral striatum drives excessive alcohol drinking. J. Neurosci. 36(39), 10116-10127 (2016).
5. A small molecule p75NTR ligand normalizes signalling and reduces Huntington’s disease phenotypes in R6/2 and BACHD mice. Hum. Mol. Genet. 25(22), 4920-4938 (2016).