venglustat   Click here for help

GtoPdb Ligand ID: 11550

Synonyms: Genz-682452 | GZ/SAR402671 | ibiglustat | SAR402671
PDB Ligand
Compound class: Synthetic organic
Comment: Venglustat is a clinical stage oral glucosylceramide synthase (GCS) inhibitor. GCS is encoded by the UGCG gene. It was developed for potential to treat diseases in which the glycolipid glucosylceramide accumulates and leads to lysosomal dysfunction and organ damage [3-4]. Venglustat inhibits glucosylceramide synthesis. Its chemical structure is claimed in Genzyme's patent WO2012129084A2 [1]. It has subsequently been reported to act as a substrate-competitive inhibitor of N-terminal Xaa-Pro-Lys N-methyltransferase 1 (NTMT1; Q9BV86; IC50 420 nM) [2].

The venglustat analogue GENZ-667161 and the eliglustat analogue GENZ-123346 have been shown to inhibit replication of SARS-CoV-2 in vitro [5], potentially by disrupting the host cell membrane dynamics which the virions depend upon for infection.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 5
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 82.7
Molecular weight 389.16
XLogP 3.27
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 O=C(NC(c1csc(n1)c1ccc(cc1)F)(C)C)O[C@@H]1CN2CCC1CC2
Isomeric SMILES O=C(NC(c1csc(n1)c1ccc(cc1)F)(C)C)O[C@@H]1CN2CCC1CC2
InChI InChI=1S/C20H24FN3O2S/c1-20(2,17-12-27-18(22-17)14-3-5-15(21)6-4-14)23-19(25)26-16-11-24-9-7-13(16)8-10-24/h3-6,12-13,16H,7-11H2,1-2H3,(H,23,25)/t16-/m1/s1
InChI Key YFHRCLAKZBDRHN-MRXNPFEDSA-N
No information available.
Summary of Clinical Use Click here for help
This clinical candidate has failed to demonstrate efficacy in Parkinson's disease and autosomal dominant polycystic kidney disease (ADPKD). Studies in Gaucher disease type 3 [6], Fabry disease [4] and GM2 gangliosidosis are still ongoing.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01674036 Safety, Tolerability and Pharmacokinetics of Genz-682452 in Healthy Men Phase 1 Interventional Sanofi
NCT01710826 A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Genz-682452 in Healthy Volunteers Phase 1 Interventional Sanofi
NCT02906020 A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of Venglustat (GZ/SAR402671) in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation Phase 2 Interventional Sanofi
NCT02228460 Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease Phase 2 Interventional Sanofi
NCT02843035 Venglustat in Combination With Cerezyme in Adult and Pediatric Patients With Gaucher Disease Type 3 Phase 2/Phase 3 Interventional Sanofi
NCT04221451 A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2 Phase 3 Interventional Sanofi
NCT04705051 Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat Phase 3 Interventional Sanofi