ziritaxestat   Click here for help

GtoPdb Ligand ID: 9561

Synonyms: compound 11 [PMID: 28414242] | GLPG-1690 | GLPG1690
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Ziritaxestat (GLPG1690) is a selective autotaxin Inhibitor [3], that was investigated for anti-fibrotic efficacy. Animal studies using GLPG1690 suggested potential for autotaxin inhibition in breast cancer treatment [2,9] and TSC2-loss associated oncogenicity (in tuberous sclerosis complex) [4]. In early 2021 data from the phase 3 ziritaxestat program in idiopathic pulmonary fibrosis (IPF; ISABELA) was analysed, and the conclusion reached was that ziritaxestat's benefit-risk profile did not support continuing the program. At that time the decision was made to discontinue the inhibitor's phase 2 trial in systemic sclerosis.
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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

ziritaxestat is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 9
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 132.48
Molecular weight 588.24
XLogP 3.62
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCc1nc2n(c1N(c1sc(c(n1)c1ccc(cc1)F)C#N)C)cc(cc2C)N1CCN(CC1)CC(=O)N1CC(C1)O
Isomeric SMILES CCc1nc2n(c1N(c1sc(c(n1)c1ccc(cc1)F)C#N)C)cc(cc2C)N1CCN(CC1)CC(=O)N1CC(C1)O
InChI InChI=1S/C30H33FN8O2S/c1-4-24-29(35(3)30-34-27(25(14-32)42-30)20-5-7-21(31)8-6-20)39-15-22(13-19(2)28(39)33-24)37-11-9-36(10-12-37)18-26(41)38-16-23(40)17-38/h5-8,13,15,23,40H,4,9-12,16-18H2,1-3H3
InChI Key REQQVBGILUTQNN-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
GLPG1690 was progressed to Phase 3 evaluation in IPF [5] and has completed a Phase 2 study in patients with scleroderma. Both of these programmes were discontinued in early 2021, due to lack of acceptable clinical benefit at intermin data analysis in the IPF study.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03711162 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 Phase 3 Interventional Galapagos NV
NCT03733444 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 Phase 3 Interventional Galapagos NV
NCT02179502 First-in-Human Single and Multiple Dose of GLPG1690 Phase 1 Interventional Galapagos NV 10
NCT02738801 Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Phase 2 Interventional Galapagos NV 6
NCT03798366 A Clinical Study to Test How Effective and Safe GLPG1690 is for Patients With Systemic Sclerosis Phase 2 Interventional Galapagos NV