LM11A-31   Click here for help

GtoPdb Ligand ID: 13391

Synonyms: LM-11A-31
Compound class: Synthetic organic
Comment: LM11A-31 is a first-in-class orally available, brain-penetrant small molecule ligand of the nerve growth factor receptor (a.k.a. p75 neurotrophin receptor, p75NTR) [2]. It inhibits proNGF-induced cell death and promotes survival signalling in vitro. It has been assessed for activity in experimental models of brain and spinal cord injury [5,7,10-11] and neurodegenerative diseases [1,3-4,8-9,12].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 67.59
Molecular weight 243.35
XLogP -0.19
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC[C@H](C)[C@@H](C(=O)NCCN1CCOCC1)N
Isomeric SMILES CC[C@H](C)[C@@H](C(=O)NCCN1CCOCC1)N
InChI InChI=1S/C12H25N3O2/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)/t10-,11-/m0/s1
InChI Key YNMUTYLWSRFTPX-QWRGUYRKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Knowles JK, Simmons DA, Nguyen TV, Vander Griend L, Xie Y, Zhang H, Yang T, Pollak J, Chang T, Arancio O et al.. (2013)
Small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer's mouse model.
Neurobiol Aging, 34 (8): 2052-63. [PMID:23545424]
2. Massa SM, Xie Y, Yang T, Harrington AW, Kim ML, Yoon SO, Kraemer R, Moore LA, Hempstead BL, Longo FM. (2006)
Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death.
J Neurosci, 26 (20): 5288-300. [PMID:16707781]
3. Nasoohi S, Tayefeh Ghahremani P, Alehossein P, Elyasizadeh S, BaniArdalan S, Ismael S, Vatanpour H, Ahmadiani A, Ishrat T. (2023)
The p75 neurotrophin receptor inhibitor, LM11A-31, ameliorates acute stroke injury and modulates astrocytic proNGF.
Exp Neurol, 359: 114161. [PMID:35787888]
4. Nguyen TV, Shen L, Vander Griend L, Quach LN, Belichenko NP, Saw N, Yang T, Shamloo M, Wyss-Coray T, Massa SM et al.. (2014)
Small molecule p75NTR ligands reduce pathological phosphorylation and misfolding of tau, inflammatory changes, cholinergic degeneration, and cognitive deficits in AβPP(L/S) transgenic mice.
J Alzheimers Dis, 42 (2): 459-83. [PMID:24898660]
5. Qin X, Wang J, Chen S, Liu G, Wu C, Lv Q, He X, Bai X, Huang W, Liao H. (2022)
Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption.
Glia, 70 (5): 892-912. [PMID:35064700]
6. Shanks HRC, Chen K, Reiman EM, Blennow K, Cummings JL, Massa SM, Longo FM, Börjesson-Hanson A, Windisch M, Schmitz TW. (2024)
p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.
Nat Med, 30 (6): 1761-1770. [PMID:38760589]
7. Shi J, Longo FM, Massa SM. (2013)
A small molecule p75(NTR) ligand protects neurogenesis after traumatic brain injury.
Stem Cells, 31 (11): 2561-74. [PMID:23940017]
8. Simmons DA, Belichenko NP, Ford EC, Semaan S, Monbureau M, Aiyaswamy S, Holman CM, Condon C, Shamloo M, Massa SM et al.. (2016)
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. [PMID:28171570]
9. Simmons DA, Knowles JK, Belichenko NP, Banerjee G, Finkle C, Massa SM, Longo FM. (2014)
A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression.
PLoS One, 9 (8): e102136. [PMID:25153701]
10. Simmons DA, Mills BD, Butler Iii RR, Kuan J, McHugh TLM, Akers C, Zhou J, Syriani W, Grouban M, Zeineh M et al.. (2021)
Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31.
Neurotherapeutics, 18 (2): 1039-1063. [PMID:33786806]
11. Tep C, Lim TH, Ko PO, Getahun S, Ryu JC, Goettl VM, Massa SM, Basso M, Longo FM, Yoon SO. (2013)
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. [PMID:23303920]
12. Yang T, Tran KC, Zeng AY, Massa SM, Longo FM. (2020)
Small molecule modulation of the p75 neurotrophin receptor inhibits multiple amyloid beta-induced tau pathologies.
Sci Rep, 10 (1): 20322. [PMID:33230162]