| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
pIC50: 8.28 ± 0.11 (GTPγS)[1]
Targets GPR84 with high potency, exhibiting a pIC50 of 8.28 +/- 0.11 for inhibiting GTPgammaS binding. It shows no activity against the related fatty acid receptors FFAR2 or FFAR3 at concentrations up to 10 microM, indicating good selectivity. |
|---|---|
| ln Vitro |
When evaluated at 10 μM, compound 42, or GPR84 antagonist 3, is unable to block the activities of the C3 fatty acid propionate at either FFAR2 or FFAR3[1].
GPR84 antagonist 3 inhibits GTPgammaS binding to GPR84 with a pIC50 of 8.28 in cell membrane-based assays. It displays no ability to block the actions of C3 fatty acid propionate at either FFAR2 or FFAR3 when tested at 10 microM, confirming its selectivity for GPR84 over these related GPCRs. |
| ln Vivo |
Compound 42, also known as GPR84 antagonist 3, exhibits an excellent elimination half-life of 2.51 hours, a moderate rate of clearance, and bioavailability at a single dose of 1 mg/kg (IV) and 10 mg/kg (Orally).
In vivo studies have shown that GPR84 antagonist 3 has a favorable pharmacokinetic profile with good oral bioavailability, moderate clearance, and an elimination half-life of 2.51 hours following oral administration. These properties make it suitable for further efficacy studies in animal models of inflammation. |
| Enzyme Assay |
Non-cell GTPgammaS binding assays are performed using membranes from cells expressing human GPR84. Membranes are incubated with [3⁵S]GTPgammaS (0.1 nM), GDP (10 microM), and test compound at various concentrations (0.1 nM-10 microM) in assay buffer for 60 min at 30degC. Bound radioactivity is separated by filtration and quantified by scintillation counting.
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| Cell Assay |
Functional assays are typically performed in CHO-K1 or HEK293 cells stably expressing human GPR84. Cells are seeded in 96-well plates and loaded with calcium indicator dye. After antagonist pre-incubation (15 min), cells are stimulated with a GPR84 agonist (e.g., 3-hydroxydecanoic acid, 1 microM) and fluorescence is measured using a FLIPR system.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6J mice (n = 3)[1]
Doses: 1 mg/kg (IV), 10 mg/kg (Orally) Route of Administration: IV, po (oral gavage) once (pharmacokinetic/PK Analysis) Experimental Results: pharmacokinetic/PK Parameters of GPR84 antagonist 3 in Male C57BL/6J mice[1]. IV (1 mg/kg) PO (10 mg/kg) half-life (h) 2.51 ± 6.55 CL (mL/min/kg) 38.9 ± 13.9 Vss (L/kg ) 7.24 ± 9.2 C0 (ng/mL) 394 ± 19.1 AUCall (ng/mL·h) 420 ± 12.5 1590 ± 18.7 Tmax (h) 1 Cmax (ng/mL) 402 ± 31.8 F (%) 36.8 ± 18.7 Pharmacokinetic studies are conducted in male SD rats or ICR mice. Animals receive a single dose of GPR84 antagonist 3 either intravenously (1 mg/kg) or orally (10 mg/kg). Blood samples are collected at multiple time points up to 24 h. Plasma concentrations are analyzed by LC-MS/MS to calculate PK parameters including t½, Cmax, Tmax, AUC, clearance, and oral bioavailability. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic parameters have been reported: good oral bioavailability, moderate clearance rate, and an elimination half-life (t½) of 2.51 hours after oral administration. The compound also shows a favorable pharmacokinetic profile suitable for in vivo efficacy studies in preclinical models.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GPR84 antagonist 3 is not publicly available. As a research-grade antagonist with a favorable PK profile, standard preclinical toxicity assessments including acute toxicity studies would be required for advancement towards clinical development.
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| References | |
| Additional Infomation |
GPR84 antagonist 3 is a research chemical not approved for clinical use. It exhibits a favorable pharmacokinetic profile suitable for in vivo studies. GPR84 is a GPCR primarily expressed on immune cells and is considered a promising target for treating inflammatory and fibrotic diseases. This compound is a valuable tool for investigating GPR84-mediated inflammatory pathways.
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| Molecular Formula |
C29H27N5O
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|---|---|
| Molecular Weight |
461.557585954666
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| Exact Mass |
461.221
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| CAS # |
2815263-05-7
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| PubChem CID |
164887573
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
643
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1COCCN1CC2=CC=C(C=C2)C3=C(N=C(N=N3)CC4=CNC5=CC=CC=C54)C6=CC=CC=C6
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| InChi Key |
XGBKJLWLVCHTCR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H27N5O/c1-2-6-22(7-3-1)28-29(23-12-10-21(11-13-23)20-34-14-16-35-17-15-34)33-32-27(31-28)18-24-19-30-26-9-5-4-8-25(24)26/h1-13,19,30H,14-18,20H2
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| Chemical Name |
4-[[4-[3-(1H-indol-3-ylmethyl)-5-phenyl-1,2,4-triazin-6-yl]phenyl]methyl]morpholine
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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: 100 mg/mL (216.66 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1666 mL | 10.8328 mL | 21.6657 mL | |
| 5 mM | 0.4333 mL | 2.1666 mL | 4.3331 mL | |
| 10 mM | 0.2167 mL | 1.0833 mL | 2.1666 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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