Venglustat

Summary

Venglustat (CHEMBL4297611) is a phase-3 clinical-stage small molecule targeting UGCG; indicated across 10 conditions including gaucher disease and cystic kidney disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (UGCG)
• Indications: 10 conditions
• Clinical trials: 18
• Chemistry: 389.5 Da · C20H24FN3O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297611
Name	Venglustat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	60199242
Molecular formula	C20H24FN3O2S
Molecular weight	389.5
InChIKey	YFHRCLAKZBDRHN-MRXNPFEDSA-N

SMILES: CC(C)(C1=CSC(=N1)C2=CC=C(C=C2)F)NC(=O)O[C@@H]3CN4CCC3CC4

IUPAC name: [(3S)-1-azabicyclo[2.2.2]octan-3-yl] N-[2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl]carbamate

Also known as: Genz-682452, GENZ-682452, GZ-402671, GZ/SAR-402671, GZ/SAR402671, Gz402671, GZ402671, Ibiglustat, SAR-402671, SAR402671, Venglustat, VENGLUSTAT

Parent form; salt/anhydrous children: CHEMBL4594270

Patent coverage: 23 distinct patent families (76 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
UGCG	UDP-glucose ceramide glucosyltransferase	Inhibition	5.3	8.4%	Q16739

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Ceramide glucosyltransferase, N-terminal Xaa-Pro-Lys N-methyltransferase 1.

Bioactivity

ChEMBL activities: 11 potent at pChembl ≥ 5 of 11 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
UGCG	7.92	IC50	12	nM	CHEMBL_ACT_24980912
NTMT1	7.49	Kd	32.5	nM	CHEMBL_ACT_24747757
UGCG	7.36	IC50	44	nM	CHEMBL_ACT_24980871
NTMT1	6.8	Kd	160	nM	CHEMBL_ACT_24747758
NTMT1	6.52	IC50	300	nM	CHEMBL_ACT_24747895
NTMT1	6.52	IC50	300	nM	CHEMBL_ACT_24747896
NTMT1	6.38	IC50	420	nM	CHEMBL_ACT_24747756
NTMT1	6.3	IC50	500	nM	CHEMBL_ACT_24747754
NTMT1	6.25	IC50	560	nM	CHEMBL_ACT_24747755
NTMT1	6.25	IC50	560	nM	CHEMBL_ACT_24747765
NTMT1	6.25	IC50	560	nM	CHEMBL_ACT_25450363

Target pathways

Aggregated over 1 target gene(s): UGCG.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	1	UGCG
Glycosphingolipid metabolism	1	UGCG
Sphingolipid metabolism	1	UGCG
Metabolism of lipids	1	UGCG
Glycosphingolipid biosynthesis	1	UGCG

Dominant GO biological processes

GO term	Targets
protein lipidation	1
glucosylceramide biosynthetic process	1
glycosphingolipid biosynthetic process	1
epidermis development	1
regulation of signal transduction	1
cell differentiation	1
keratinocyte differentiation	1
leptin-mediated signaling pathway	1
neuron development	1
establishment of skin barrier	1
intestinal lipid absorption	1
cornified envelope assembly	1
lipid metabolic process	1
sphingolipid metabolic process	1

Indications & clinical

Indications

10 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
Gaucher disease	3	MONDO:0018150	Orphanet:77259
cystic kidney disease	3	MONDO:0002473	EFO:0008615
Fabry disease	3	MONDO:0010526	MONDO:0010526
Sandhoff disease	3	MONDO:0010006	MONDO:0010006
Tay-Sachs disease	3	MONDO:0010100	MONDO:0010100
autosomal dominant polycystic kidney disease	2	MONDO:0004691	EFO:1001496
Parkinson disease	2	MONDO:0005180	MONDO:0005180
parkinsonian disorder	1	MONDO:0021095	HP:0001300

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE1	8
PHASE3	5
PHASE2	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05206773	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease
NCT05222906	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3
NCT05280548	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease
NCT03523728	PHASE2/PHASE3	TERMINATED	A Medical Research Study Designed to Determine if Venglustat Can be a Future Treatment for ADPKD Patients
NCT04221451	PHASE3	TERMINATED	A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT02843035	PHASE2	ACTIVE_NOT_RECRUITING	Venglustat in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3 With Venglustat Monotherapy Extension
NCT02228460	PHASE2	COMPLETED	Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-naïve Adult Male Patients With Fabry Disease
NCT02489344	PHASE2	COMPLETED	Evaluation of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-Naïve Adult Male Patients With Fabry Disease
NCT02906020	PHASE2	TERMINATED	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
NCT01674036	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetics of Genz-682452 in Healthy Men
NCT01710826	PHASE1	COMPLETED	A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Genz-682452 in Healthy Volunteers
NCT03687554	PHASE1	COMPLETED	Effect of Venglustat in Patients With Renal Impairment
NCT05238714	PHASE1	COMPLETED	Excretion Balance, Pharmacokinetics, and Metabolism Following of [14C]-Venglustat Administration in Healthy Male Subjects
NCT05718258	PHASE1	COMPLETED	A Study in Adults to Investigate the Impact of Mild, Moderate, and Severe Hepatic Impairment on Pharmacokinetics of Venglustat Compared to Participants With Normal Hepatic Function
NCT06418607	PHASE1	COMPLETED	A Study of the Safety, Tolerability, and Bioequivalence of Orally Administered Venglustat in Healthy Adult Participants
NCT06418620	PHASE1	COMPLETED	A Study of the Safety, Tolerability, and Bioavailability of Orally Administered Venglustat in Healthy Adult Participants
NCT06421714	PHASE1	COMPLETED	A Study of the Safety, Tolerability, and Pharmacokinetics of Orally Administered Venglustat and Itraconazole in Healthy Adult Male Participants

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
ELIGLUSTAT	ChEMBL + PubChem	Phase 4 (approved)	UGCG
MIGLUSTAT	ChEMBL + PubChem	Phase 4 (approved)	UGCG
LUCERASTAT	ChEMBL	Phase 3	UGCG
NIZUBAGLUSTAT	ChEMBL	Phase 2	UGCG
Migalastat	PubChem	Approved	UGCG
Miglitol	PubChem	Approved	UGCG