ambroxol   

GtoPdb Ligand ID: 10692

ambroxol is an approved drug
Compound class: Synthetic organic
Comment: Ambroxol stimulates the synthesis and release of surfactant in the respiratory tract and acts as a mucoactive/expectorant drug. This action appears to be associated with ambroxol's regulation of glucosylceramide levels, via modulation of non-lysosomal glucosylceramidase (GCase) beta 2 (GBA2; Q9HCG7). Ambroxol is reported to act as a small molecule chaperone for GCase proteins that can increase the stability and function of mutant and wild-type GCases in in vitro and in vivo models [4-5,7-8,15], and in clinical trial subjects [12,16]. Ambroxol binds to nascent GCase proteins (at the enzyme active site) within the endoplasmic reticulum, and this action facilitates transport to the lysosome [1,4]. The acidic lysosomal environment provokes ambroxol dissassociation, leaving the enzyme free to function normally.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 58.28
Molecular weight 375.98
XLogP 2.9
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES OC1CCC(CC1)NCc1cc(Br)cc(c1N)Br
Isomeric SMILES OC1CCC(CC1)NCc1cc(Br)cc(c1N)Br
InChI InChI=1S/C13H18Br2N2O/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10/h5-6,10-11,17-18H,1-4,7,16H2
InChI Key JBDGDEWWOUBZPM-UHFFFAOYSA-N
No information available.
Summary of Clinical Use
In some jurisdictions ambroxol is used as an orally delivered expectorant drug [3]. It is not yet authorised for use by the FDA or the EMA (but is approved by individual European agencies). Clinical evaluation as an expectorant are ongoing for future US approval.
Ambroxol (as the hydrochloride) is being repurposed as a novel candidate for neurodegenerative diseases including Parkinson's disease (in particular in patients with defective β-glucocerebrosidase GBA1 genes [10,13]) [7,14] and amyotrophic lateral sclerosis (ALS; motor neurone disease; MND) [2,6]. Click here to link to ClinicalTrials.gov's full list of ambroxol studies. In July 2018, the EMA granted orphan designation for ambroxol hydrochloride to be used as a treatment for ALS/MND.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02914366 Ambroxol as a Treatment for Parkinson's Disease Dementia Phase 2 Interventional Lawson Health Research Institute
NCT03843541 A Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily, Ambroxol Hydrochloride 30 mg Twice Daily and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions Phase 3 Interventional Zambon SpA
NCT02941822 Ambroxol in Disease Modification in Parkinson Disease Phase 2 Interventional University College, London