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.
Chemical Formula: C12H27Cl2N3O2
Molecular Weight: 316.267
Elemental Analysis: C, 45.57; H, 8.61; Cl, 22.42; N, 13.29; O, 10.12
Chemical Name: (2S,3S)-2-amino-3-methyl-N-[2-(4-morpholinyl)ethyl]-pentanamide, dihydrochloride
InChi Code: 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
LM11A-31 (oral gavage; 50 mg kg/day for 4 weeks) significantly mitigates proNGF accumulation and preserves BRB integrity.
LM11A-31 (orally; 50 or 75 mg/kg) administered for 3 months starting at 6-8 months of age prevents and/or reverses atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites in mid-stage male APPL/S mice.
Xie Y, Seawell J, Boesch E, Allen L, Suchy A, Longo FM, Meeker RB. Small molecule modulation of the p75 neurotrophin receptor suppresses age- and genotype-associated neurodegeneration in HIV gp120 transgenic mice. Exp Neurol. 2020 Sep 29;335:113489. doi: 10.1016/j.expneurol.2020.113489. Epub ahead of print. PMID: 33007293.
Yang T, Liu H, Tran KC, Leng A, Massa SM, Longo FM. Small-molecule modulation of the p75 neurotrophin receptor inhibits a wide range of tau molecular pathologies and their sequelae in P301S tauopathy mice. Acta Neuropathol Commun. 2020 Sep 5;8(1):156. doi: 10.1186/s40478-020-01034-0. PMID: 32891185; PMCID: PMC7487850.
McGregor C, Sabatier M, English A. Early regeneration of axons following peripheral nerve injury is enhanced if p75NTR is eliminated from the surrounding pathway. Eur J Neurosci. 2020 Aug 19. doi: 10.1111/ejn.14943. Epub ahead of print. PMID: 32812660.
Foerster Y, Stöver T, Wagenblast J, Diensthuber M, Balster S, Gabrielpillai J, Petzold H, Geissler C. Relevance of Neurotrophin Receptors CD271 and TrkC for Prognosis, Migration, and Proliferation in Head and Neck Squamous Cell Carcinoma. Cells. 2019 Sep 28;8(10):1167. doi: 10.3390/cells8101167. PMID: 31569361; PMCID: PMC6830344.
Elshaer SL, Alwhaibi A, Mohamed R, Lemtalsi T, Coucha M, Longo FM, El-Remessy AB. Modulation of the p75 neurotrophin receptor using LM11A-31 prevents diabetes-induced retinal vascular permeability in mice via inhibition of inflammation and the RhoA kinase pathway. Diabetologia. 2019 Aug;62(8):1488-1500. doi: 10.1007/s00125-019-4885-2. Epub 2019 May 9. PMID: 31073629.
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