arimoclomol   Click here for help

GtoPdb Ligand ID: 8271

Synonyms: BRX-220 | BRX220 | Miplyffa®
Approved drug
arimoclomol is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Arimoclomol is an oral therapeutic candidate for the treatment of amyotrophic lateral sclerosis (ALS). Arimoclomol may be delivered as the citrate salt (BRX-345 with PubChem CID 72710735)
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 2
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 72
Molecular weight 313.12
XLogP 2.49
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 OC(CN1CCCCC1)CON=C(c1ccc[n+](c1)[O-])Cl
Isomeric SMILES O[C@H](CN1CCCCC1)CO/N=C(/c1ccc[n+](c1)[O-])\Cl
InChI InChI=1S/C14H20ClN3O3/c15-14(12-5-4-8-18(20)9-12)16-21-11-13(19)10-17-6-2-1-3-7-17/h4-5,8-9,13,19H,1-3,6-7,10-11H2/b16-14-/t13-/m1/s1
InChI Key SGEIEGAXKLMUIZ-XUVDNFPMSA-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/)
No information available.
Summary of Clinical Use Click here for help
The EMA and FDA have granted arimoclomol orphan drug status for the treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS, aka Lou Gehrig's disease). A Phase 2/III clinical trial assessing arimoclomol in ALS (NCT00706147) is ongoing. The FDA approved arimoclomol in September 2024, to treat the neurological manifestations of the ultra-rare progressive and fatal neurodegenerative condition Niemann-Pick disease type C in combination with miglustat (a glucosylceramide synthase inhibitor) [8].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Arimoclomol acts as a coinducer of heat shock proteins (Hsps) [3] and this action has been reported to slow the process of motor neuron death and extend life in cellular and whole animal models of ALS [2,4-6,9]. Arimoclomol is reported to prolong the activation of heat shock transcription factor 1 (HSF1; Q00613), the master regulator of stress-inducible Hsps, including Hsp70 and Hsp90 [3]. Increased Hsp70 expression is believed to be responsible for the neuroprotective effect of arimoclomol in ALS mice [7]. In Niemann-Pick disease type C (NPC) lysosomes are damaged by accumulation of unesterified cholesterol due to misfolded NPC protein (NPC1). Arimoclomol appears to improve lysosome function via different pathways; increased activation of transcription factors (EB/TFEB and E3/TFE3) and upregulated expression of coordinated lysosomal expression and regulation (CLEAR [10]) genes; amplified heat shock protein (stress) response to misfolded NPC protein to improve transport of unesterified cholesterol out of lysosomes.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00706147 Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis Phase 2/Phase 3 Interventional University of Miami
NCT03491462 Arimoclomol in Amyotropic Lateral Sclerosis Phase 3 Interventional ZevraDenmark 1
NCT02612129 Arimoclomol Prospective Study in Participants Diagnosed With Niemann-Pick Disease Type C Phase 2/Phase 3 Interventional ZevraDenmark