ambroxol   Click here for help

GtoPdb Ligand ID: 10692

Approved drug
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 [4-5,7-8,17], and in clinical trial subjects [12,18]. 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 disassociation, leaving the enzyme free to function normally.

SARS-CoV-2 and COVID-19: Evidence presented in a preprint suggests that ambroxol (and its prodrug bromhexine) directly disrupts the protein-protein interaction between the SARS-CoV-2 spike protein and ACE2 [14]. This action is reported to inhibit the cytopathic effects induced by SARS-CoV-2 infection in vitro, which is suggestive of potential prophylactic and/or therapeutic use of these drugs against COVID-19.
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 CDK toolkit. 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 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
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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.

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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
Bioactivity Comments
Ambroxol behaves as an inhibitory GCase chaperone at neutral pH, so within acellular human CSF it produces an inhibitory effect on GCase activity [11]. In contrast, within cells and their acidic lysosomes ambroxol increases intracellular GCase activity by elevating the enzyme mass that reaches the lysosomes [8-9].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
glucosylceramidase beta Hs None Binding - - - 5
⤷ [5]