| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
GLPG1205 primarily targets GPR84, a G protein-coupled receptor that is activated by medium-chain fatty acids and is involved in inflammatory responses. By acting as a potent antagonist with an IC50 of 54 nM, GLPG1205 blocks GPR84-mediated signaling. This leads to anti-inflammatory effects. The compound has been studied for its potential in treating pulmonary fibrosis, where inflammation plays a key role. Its favorable PK/PD profile supports its therapeutic potential.
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| ln Vitro |
Neutrophils that are stimulated by ZQ16 to produce [Ca2+]i respond entirely to GLPG1205 (0.5 μM) [1]. The ROS response caused by GPR84 agonist is totally blocked by GLPG1205 (1 μM) when applied for 5 minutes [1]. ZQ16-induced ROS can be successfully countered by GLPG1205, as demonstrated by its IC50 value of 15 nM in TNF-primed neutrophils[1].
In vitro, GLPG1205 functions as a potent and selective GPR84 antagonist. It inhibits GTPγS binding induced by 3,3'-diindolylmethane (DIM) in cells overexpressing human GPR84 with an IC50 of 54 nM. Its activity is typically evaluated using receptor binding and functional assays measuring GTPγS binding or downstream signaling pathways. The compound's selectivity for GPR84 over other receptors is assessed. Its anti-inflammatory activity is evaluated in cellular models of inflammation. |
| ln Vivo |
In a model of idiopathic pulmonary fibrosis, GLPG1250 (orally given; 30 mg/kg; twice daily) dramatically decreased Ashcroft scores commencing 7 days after challenge and continuing for 2 weeks [3]. ? In mice, GLPG1250 (given orally at a dose of 30 mg/kg once day) dramatically decreased lung deposition beginning eighteen weeks after radiation. Moreover, GLPG1250 prevents lung bronchial epithelial cells and parenchymal macrophages from increasing MnSOD in a radiation model [3]. ? GLPG1205 dose-dependently decreased colonic MPO levels, neutrophil influx, disease activity, and histopathological activity in a mouse model of IBD [4].
In vivo, GLPG1205 is orally active and has anti-inflammatory activity. It is used for the treatment of pulmonary fibrosis. The compound shows a favorable PK/PD profile. However, specific in vivo efficacy data, including dosing regimens and animal models, are not extensively detailed in the available literature. Further studies are needed to fully characterize its in vivo pharmacological profile. The compound is a research tool for studying GPR84 and inflammation. |
| Enzyme Assay |
Cell-free assays for GLPG1205 involve evaluating its binding affinity and functional activity at GPR84. Radioligand binding assays are performed using membrane preparations from cells expressing human GPR84. GTPγS binding assays are used to measure receptor activation and inhibition. GLPG1205 is incubated with membranes and a radiolabeled ligand, and IC50 values are determined from competition curves (IC50 = 54 nM). The compound's chemical purity and identity are confirmed by HPLC and NMR analysis.
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| Cell Assay |
In vitro cellular assays for GLPG1205 typically involve treating cells overexpressing human GPR84 with various concentrations of the compound. GTPγS binding is measured to assess receptor activity. Functional assays such as calcium flux or cAMP accumulation may also be used. The compound's ability to inhibit GPR84-mediated signaling is assessed. Anti-inflammatory activity is evaluated in macrophage cell lines by measuring cytokine production. Cytotoxicity is assessed using standard cell viability assays.
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| Animal Protocol |
In vivo animal studies for GLPG1205 are conducted in models of pulmonary fibrosis and inflammation. The compound is administered orally. Lung fibrosis is assessed by histological analysis and measurement of collagen deposition. Inflammatory markers in bronchoalveolar lavage fluid and lung tissues are measured. However, specific dosing regimens and experimental protocols are not extensively documented in the available literature. Standard protocols for evaluating anti-fibrotic agents would typically be employed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GLPG1205 include a molecular weight of 378.42 g/mol, molecular formula C22H22N2O4, and purity >99%. It is soluble in DMSO (150 mg/mL). The compound is stable as a powder at -20°C for 3 years or at 4°C for 2 years; in solvent, it is stable at -80°C for 6 months or at -20°C for 1 month. It shows a favorable PK/PD profile. Detailed ADME parameters are not extensively reported.
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| Toxicity/Toxicokinetics |
The toxicity profile of GLPG1205 has been characterized in preclinical studies. As a GPR84 antagonist, potential toxicities may include effects on immune function and metabolic regulation. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
GLPG-1205 is being investigated in the clinical trial NCT03725852 (a clinical study designed to test the efficacy and safety of GLPG1205 in patients with idiopathic pulmonary fibrosis (IPF)).
GLPG1205 is a potent, selective, and orally active GPR84 antagonist with an IC50 of 54 nM. It has anti-inflammatory activity and is used for the treatment of pulmonary fibrosis. Its molecular formula is C22H22N2O4 with a molecular weight of 378.42 g/mol. GLPG1205 shows a favorable PK/PD profile. It is a research tool for studying GPR84 and inflammation. |
| Molecular Formula |
C22H22N2O4
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|---|---|
| Molecular Weight |
378.421085834503
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| Exact Mass |
378.157
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| CAS # |
1445847-37-9
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| PubChem CID |
71616860
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
757
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CCOC[C@H]1COC1C=C2C3C=CC(C#CC4CC4)=CC=3CCN2C(N=1)=O
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| InChi Key |
IRBAWVGZNJIROV-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C22H22N2O4/c25-22-23-21(28-14-18-13-26-9-10-27-18)12-20-19-6-5-16(4-3-15-1-2-15)11-17(19)7-8-24(20)22/h5-6,11-12,15,18H,1-2,7-10,13-14H2/t18-/m0/s1
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| Chemical Name |
(S)-2-((1,4-dioxan-2-yl)methoxy)-9-(cyclopropylethynyl)-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one
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| Synonyms |
GLPG1205 GLPG 1205 GLPG-1205
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
DMSO : ~250 mg/mL (~660.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 6.25 mg/mL (16.52 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 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. Solubility in Formulation 2: ≥ 6.25 mg/mL (16.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (13.21 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6426 mL | 13.2128 mL | 26.4257 mL | |
| 5 mM | 0.5285 mL | 2.6426 mL | 5.2851 mL | |
| 10 mM | 0.2643 mL | 1.3213 mL | 2.6426 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.
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