Ziritaxestat

Summary

Ziritaxestat (CHEMBL3828074) is a phase-3 clinical-stage small molecule targeting ENPP2; indicated across 3 conditions including idiopathic pulmonary fibrosis and systemic sclerosis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (ENPP2)
• Indications: 3 conditions
• Clinical trials: 8
• Chemistry: 588.7 Da · C30H33FN8O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3828074
Name	Ziritaxestat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	90420193
Molecular formula	C30H33FN8O2S
Molecular weight	588.7
InChIKey	REQQVBGILUTQNN-UHFFFAOYSA-N

SMILES: CCC1=C(N2C=C(C=C(C2=N1)C)N3CCN(CC3)CC(=O)N4CC(C4)O)N(C)C5=NC(=C(S5)C#N)C6=CC=C(C=C6)F

IUPAC name: 2-[[2-ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]-methylamino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile

Also known as: G-451990, G451990, GLPG-1690, Glpg1690, GLPG1690, Ziritaxestat, Ziritaxestatn, ZIRITAXESTAT, ZIRITAXESTATN, ZIRITAXESTAT (GLPG1690), Galapagos

Patent coverage: 160 distinct patent families (524 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
ENPP2	autotaxin	Inhibition	7.82	0.6%	Q13822

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Autotaxin, Autotaxin, Autotaxin.

Bioactivity

ChEMBL activities: 25 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ENPP2	11	IC50	0.01	nM	CHEMBL_ACT_16654602
ENPP2	8.89	IC50	1.3	nM	CHEMBL_ACT_20653689
ENPP2	8.54	IC50	2.9	nM	CHEMBL_ACT_23153552
ENPP2	8.54	IC50	2.9	nM	CHEMBL_ACT_24791997
ENPP2	8.51	IC50	3.1	nM	CHEMBL_ACT_22850742
ENPP2	8.43	IC50	3.7	nM	CHEMBL_ACT_22973250
ENPP2	8.41	IC50	3.9	nM	CHEMBL_ACT_24918047
ENPP2	8.3	IC50	5	nM	CHEMBL_ACT_28485353
ENPP2	7.82	Ki	15	nM	CHEMBL_ACT_18239169
ENPP2	7.3	IC50	50	nM	CHEMBL_ACT_28426841
ENPP2	7.13	IC50	73.4	nM	CHEMBL_ACT_25958216
ENPP2	7	IC50	100	nM	CHEMBL_ACT_16654605
ENPP2	7	IC50	100	nM	CHEMBL_ACT_17984841
ENPP2	6.88	IC50	131	nM	CHEMBL_ACT_16654600
ENPP2	6.88	IC50	131	nM	CHEMBL_ACT_18239189
ENPP2	6.88	IC50	131	nM	CHEMBL_ACT_20653710
Q64610	6.88	IC50	131	nM	CHEMBL_ACT_24918855
ENPP2	6.7	IC50	200	nM	CHEMBL_ACT_25559135
Q9R1E6	6.65	IC50	224	nM	CHEMBL_ACT_16654599
ENPP2	6.62	IC50	242	nM	CHEMBL_ACT_18239111
ENPP2	6.52	IC50	300	nM	CHEMBL_ACT_26743423
ENPP2	6.52	IC50	300	nM	CHEMBL_ACT_27841676
ENPP2	6.52	IC50	300	nM	CHEMBL_ACT_28426208
Q9R1E6	6.38	IC50	418	nM	CHEMBL_ACT_18239173
Q64610	6.27	IC50	542	nM	CHEMBL_ACT_18239109

Target pathways

Aggregated over 1 target gene(s): ENPP2.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Vitamin B5 (pantothenate) metabolism	1	ENPP2

Dominant GO biological processes

GO term	Targets
chemotaxis	1
immune response	1
phospholipid catabolic process	1
positive regulation of epithelial cell migration	1
sphingolipid catabolic process	1
regulation of cell migration	1
phosphatidylcholine catabolic process	1
positive regulation of lamellipodium morphogenesis	1
lipid metabolic process	1
phospholipid metabolic process	1
lipid catabolic process	1
vesicle-mediated transport	1
cell motility	1
positive regulation of peptidyl-tyrosine phosphorylation	1

Indications & clinical

Indications

3 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
idiopathic pulmonary fibrosis	3	MONDO:0800504	EFO:0000768
systemic sclerosis	2	MONDO:0005100	EFO:0000717

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

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE1	4
PHASE3	2
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03711162	PHASE3	TERMINATED	A Clinical Study to Test How Effective and Safe GLPG1690 is for Subjects With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care
NCT03733444	PHASE3	TERMINATED	A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Idiopathic Pulmonary Fibrosis (IPF) When Used Together With Standard of Care
NCT03798366	PHASE2	COMPLETED	A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Systemic Sclerosis
NCT03976648	PHASE2	TERMINATED	A Clinical Study to Test Long Term Safety of GLPG1690 for Patients With Systemic Sclerosis
NCT02179502	PHASE1	COMPLETED	First-in-Human Single and Multiple Dose of GLPG1690
NCT03143712	PHASE1	COMPLETED	Study to Assess Bioavailability of GLPG1690 Given as Oral Capsule or Tablet
NCT03515382	PHASE1	COMPLETED	A Study in Healthy Male Volunteers to Look at How the Test Medicine GLPG1690 is Taken up by the Body When Doses of Itraconazole and Voriconazole Are Given to Healthy Volunteers
NCT03787186	PHASE1	COMPLETED	A Study in Healthy Male Volunteers to Look at How the Test Medicine GLPG1690 is Taken up by the Body When Given by Mouth and Into a Vein as an Injection

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
DRONABINOL	ChEMBL + PubChem	Phase 4 (approved)	ENPP2
EVANS BLUE	ChEMBL	Phase 4 (approved)	ENPP2
TAURURSODIOL	ChEMBL	Phase 4 (approved)	ENPP2
URSODIOL	ChEMBL	Phase 4 (approved)	ENPP2
CAMBRITAXESTAT	ChEMBL	Phase 2	ENPP2
CUDETAXESTAT	ChEMBL	Phase 2	ENPP2