LM11A-31 HCl

• CAS: 1243259-19-9
• Catalog Number: ACM1243259199
• Category: Antagonists
• Molecular Weight: 316.27
• Molecular Formula: C12H27Cl2N3O2
• Description: LM11A-31 is a small-molecule p75NTR modulator and proNGF antagonist, in preventing diabetes-induced BRB breakdown. Targeting p75NTR signalling using LM11A-31, an orally bioavailable receptor modulator, may offer an effective, safe and non-invasive therapeutic strategy for treating macular oedema, a major cause of blindness in diabetes.
• Synonyms: LM11A-31 HCl; LM11A-31 hydrochloride; LM11A-31; LM11A 31; LM11A31; LM 11A-31; LM 11A31; LM-11A-31
• IUPAC Name: (2S,3S)-2-amino-3-methyl-N-[2-(4-morpholinyl)ethyl]-pentanamide, dihydrochloride
• Canonical SMILES: CC[C@H](C)[C@H](N)C(NCCN1CCOCC1)=O.[H]Cl.[H]Cl
• InChI: InChI=1S/C12H25N3O2.2ClH/c1-3-10(2)11(13)12(16)14-4-5-15-6-8-17-9-7-15;;/h10-11H,3-9,13H2,1-2H3,(H,14,16);2*1H/t10-,11-;;/m0../s1
• InChI Key: LLIHJRRZJDEKLB-ULEGLUPFSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1243259-19-9 (HCl); 102562-74-3 (free base)
• Biological Target: LM11A-31 dihydrochloride, a non-peptide p75NTR (neurotrophin receptor p75) modulator, is a potent proNGF (nerve growth factor) antagonist.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 45.57; H, 8.61; Cl, 22.42; N, 13.29; O, 10.12
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To test the effects of LM11A-31 in the presence of FIV (feline immunodeficiency virus), feline neural cultures at 12 days in culture were inoculated with 105 TCID50 FIV mix followed immediately by addition of LM11A-31 at a concentration of 10 nM. LM11A-31 was sustained in the culture throughout the experiment and the cells were fixed at 3 and 7 days post-treatment and stained for MAP-2 and GFAP. The FIV inoculated cultures showed damage after seven days which is illustrated in Figure 3A. Beading and simplification of MAP-2+ processes and neuron shrinkage was seen as in Figure 1 and a co-stain for GFAP stain also showed a retraction of astrocyte processes with development of a more process bearing morphology. Treatment with LM11A-31 reversed much of this damage with most cultures showing healthy neurons with elaborate processes on a more uniform bed of astrocytes (Figure 3B). Quantification of the MAP-2 stain shown in Figure 4, illustrates the mean (± sem) MAP-2 fluorescence intensity relative to untreated control cultures at three days and seven days post-inoculation. At three days no decrease in MAP-2 stain or changes in neuron morphology were seen (94.8 ± 7.1% of control) and by seven days a 58% decrease was seen (41.8 ± 15.7% of control, p=0.0049). In each case, treatment with LM11A-31 resulted in MAP-2 staining that was above the control values (172-193%) and 4-fold greater than the MAP-2 intensity of the neural cultures treated with FIV (FIV+LM11A-31 vs. FIV at 7 days, p=0.0111). The strong neuroprotection afforded by LM11A-31 in an infectious in vitro model indicates that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration.; Rerference: J Neuroimmune Pharmacol. 2012 Jun; 7(2): 388-400. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746485/
• In Vivo Activity: To further assess the robustness of the effect of LM11A-31 in slowing progression of degeneration due to Alzheimer's disease (AD), it was determined whether the ligand would be effective in reducing neurite degeneration in another well-characterized AD mouse model, Tg2576 mice. LM11A-31 was administered to female Tg2576 mice and their nTg littermates for 3 months starting at 14 months of age. In these mice, cognitive deficits are seen at 3 months of age and are progressive. Insoluble Aβ levels incrementally increase beginning at 6 months of age and Aβ deposition is evident at 11 months. Cholinergic dystrophic neurites are not seen at 8 months of age but occur in the cortex by 16 months. In comparison to nTg mice, vehicle-treated Tg2576 mice at 17 months old had shorter ChAT-stained neurites in the basal forebrain that occupied less area (Fig. 10A,B). These deficits were prevented in Tg2576 mice given LM11A-31, which had cholinergic neurites resembling those of nTg mice. Dendrite branching complexity was also decreased in vehicle-treated Tg2576 mice but not in those given LM11A-31, compared to nTg mice (Fig. 10C). Finally, LM11A-31 did not affect the number of cholinergic dystrophic neurite clusters in the cortex, but significantly reduced the total area they occupied as well as the mean area per cluster (Fig. 10D-F). LM11A-31 did not affect any measure in nTg mice. These findings confirmed the ability of LM11A-31 treatment to prevent neurite degeneration in a second mouse model.; Reference: PLoS One. 2014; 9(8): e102136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143160/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).