Ziritaxestat

An investigational drug for idiopathic pulmonary fibrosis

{{Drugbox | verifiedfields = changed | verifiedrevid = 123456789 | IUPAC_name = (2S)-2-[[4-[[2-(2,3-dihydro-1H-inden-2-yl)ethyl]amino]-6-[[2-(1H-tetrazol-5-yl)ethyl]amino]-1,3,5-triazin-2-yl]amino]butanoic acid | image = Ziritaxestat.svg | image2 = | width = 200 | alt = | tradename = | synonyms = GLPG1690 | CAS_number = 1447011-42-5 | ATC_prefix = | ATC_suffix = | PubChem = 71587780 | DrugBank = DB15151 | ChemSpiderID = 34980963 | UNII = 3F0K3T4Q3F | KEGG = D11468 | ChEMBL = 3545118 | IUPHAR_ligand = 10001 | SMILES = CC(C)C(C(=O)O)NC1=NC(=NC(=N1)NCC2=CC3=C(C=C2)CCC3)NCC4=NNN=N4 | StdInChI = 1S/C22H29N9O2/c1-15(2)19(22(32)33)28-21-26-18(25-20(27-21)24-12-16-8-9-17-6-4-5-7-17)23-11-14-3-10-13-18-14/h3,8-10,13,15-16,19H,4-7,11-12H2,1-2H3,(H,28,32,33)(H,23,24,25,26,27) | StdInChIKey = QWZKQXJZQXJZQX-UHFFFAOYSA-N }}

Ziritaxestat (development code GLPG1690) is an investigational drug that was being developed for the treatment of idiopathic pulmonary fibrosis (IPF). It is a small molecule inhibitor of the enzyme autotaxin, which is involved in the production of lysophosphatidic acid (LPA), a lipid mediator implicated in the pathogenesis of fibrosis.

Mechanism of Action

Ziritaxestat functions by inhibiting the activity of autotaxin, an enzyme that catalyzes the conversion of lysophosphatidylcholine to LPA. LPA is known to promote fibrosis by stimulating fibroblast proliferation and collagen production. By reducing LPA levels, ziritaxestat aims to mitigate the fibrotic processes that characterize IPF.

Clinical Development

Ziritaxestat was in clinical development for the treatment of IPF, a chronic and progressive lung disease characterized by the scarring of lung tissue. The drug was evaluated in several clinical trials to assess its safety, tolerability, and efficacy in patients with IPF.

Phase I Trials

Initial phase I trials focused on assessing the safety and pharmacokinetics of ziritaxestat in healthy volunteers. These studies helped establish the appropriate dosing regimen for subsequent trials.

Phase II Trials

In phase II trials, ziritaxestat demonstrated promising results in reducing biomarkers associated with fibrosis and showed potential in slowing the progression of IPF. These trials provided the basis for advancing the drug into phase III studies.

Phase III Trials

Ziritaxestat entered phase III clinical trials to further evaluate its efficacy and safety in a larger cohort of IPF patients. However, the development of ziritaxestat was discontinued after interim analysis indicated that the benefit-risk profile did not support continuation.

Discontinuation

In January 2021, the development of ziritaxestat was halted following a recommendation from the Independent Data Monitoring Committee. The decision was based on an interim analysis of the phase III ISABELA trials, which suggested that the potential benefits of the drug did not outweigh the risks.

Related Pages

• Idiopathic pulmonary fibrosis
• Autotaxin
• Lysophosphatidic acid