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Purity: ≥98%
Ziritaxestat (formerly GLPG1690) is a potent and a first-in-class selective autotaxin (ATX) inhibitor (IC50 = 131 nM and Ki of 15 nM) with the potential to be used in the treatment of idiopathic pulmonary disease (IPF). As of Feb 2021, the phase 3 trial has failed. GLPG1690 showed improved pharmacokinetic properties with a low plasma clearance and high bioavailability in mouse and rat. The good pharmacokinetic profile is further confirmed in dog, with GLPG1690 showing low plasma clearance (0.12 L/h/kg) and a high bioavailability (63%). In a Phase 1 study, GLPG1690 demonstrated favorable safety and tolerability profile, as well as a strong pharmacodynamic signal implying target engagement.
| ln Vitro |
Ziritaxestat (GLPG1690) exhibits a 15 μM IC50 in manual patch clamp experiments, with no CYP3A4 TDI and decreased hERG inhibitory activity [1].
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| ln Vivo |
With IC50 values of 418 nM, 542 nM, and 242 nM, respectively, ziritaxestat (GLPG1690) inhibits ATX-induced LPA 18:2 production in the plasma of mice, rats, and healthy donors in a concentration-dependent manner. In mice and rats, ziritaxestat (GLPG1690) demonstrates enhanced pharmacokinetic characteristics, including low plasma clearance and high bioavailability. Ziritaxestat (GLPG1690) exhibits a favorable pharmacokinetic profile, as evidenced by its low plasma clearance (0.12 L/h/kg) and high bioavailability (63%).
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| References |
[1]. Desroy N, et al. Discovery of 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)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem. 2017 May 11;60(9):3580-3590.
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| Molecular Formula |
C30H33FN8O2S
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| Molecular Weight |
588.71
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| CAS # |
1628260-79-6
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| Related CAS # |
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| SMILES |
N#CC1=C(C2=CC=C(F)C=C2)N=C(N(C3=C(CC)N=C4C(C)=CC(N5CCN(CC(N6CC(O)C6)=O)CC5)=CN43)C)S1
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.25 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6986 mL | 8.4931 mL | 16.9863 mL | |
| 5 mM | 0.3397 mL | 1.6986 mL | 3.3973 mL | |
| 10 mM | 0.1699 mL | 0.8493 mL | 1.6986 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Figure 6. Activity of compounds in mouse BLM model: Ashcroft score (Matsuse’s modification) at day 21.J Med Chem.2017 May 11;60(9):3580-3590. |
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Figure 5. Mean (±SEM) plasma exposure of11and LPA 18:2 reduction after single oral doses of 3, 10, and 30 mg/kg in mice (n= 3).J Med Chem.2017 May 11;60(9):3580-3590. |
Figure 7. Analysis of LPA 18:2 in BALF of PBS-challenged mice (n= 9) or BLM-challenged mice treated either with vehicle (n= 6) or compound11(30 mg/kg twice daily,n= 7) for 21 days.J Med Chem.2017 May 11;60(9):3580-3590. |
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