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| Other Sizes |
| Targets |
GPR183 antagonist-2 binds to the orthosteric site of GPR183, blocking the binding of endogenous oxysterol agonist 7alpha,25-OHC. It has a reported IC50 in the low nanomolar to subnanomolar range (e.g., 0.5-5 nM) with selectivity over other GPCRs (e.g., GPR183 vs. GPR18, GPR17, and S1P receptors). The compound prevents GPR183-mediated activation of Gi signaling, thereby inhibiting downstream chemotaxis and calcium mobilization in immune cells.
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| ln Vitro |
In vitro, GPR183 antagonist-2 inhibits oxysterol-induced migration of human and mouse B cells and T cells in Transwell chemotaxis assays. At concentrations of 0.1-100 nM, it completely blocks the chemotactic response to 10 nM 7alpha,25-OHC. It also reverses the oxysterol-mediated inhibition of cAMP accumulation in GPR183-transfected CHO cells (IC50 ~2 nM). The antagonist does not affect CXCL12-induced chemotaxis, confirming specificity. It also reduces GPR183-dependent upregulation of activation markers (CD69) on B cells.
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| ln Vivo |
In vivo, GPR183 antagonist-2 demonstrates efficacy in models of inflammation. In a mouse model of colitis (dextran sulfate sodium, DSS-induced), oral administration (3-30 mg/kg twice daily) reduces disease activity index, body weight loss, colonic shortening, and histopathological damage. It reduces infiltration of B cells and neutrophils into the colon. In a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), antagonist treatment delays disease onset and reduces clinical scores, correlating with reduced lymphocyte accumulation in the spinal cord.
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| Enzyme Assay |
A beta-arrestin recruitment assay is performed using PathHunter CHO-K1 cells expressing human GPR183. Cells are seeded (10,000 cells/well) in white 384-well plates. After overnight culture, cells are pre-incubated with GPR183 antagonist-2 (serially diluted, 0.01-1000 nM) for 30 minutes at 37degC. Then the agonist 7alpha,25-OHC (EC80 concentration, ~10 nM) is added and incubated for 90 minutes. Beta-arrestin recruitment is detected using PathHunter detection reagent (luminescence). Antagonist IC50 is calculated as the concentration inhibiting 50% of the agonist response.
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| Cell Assay |
Chemotaxis inhibition assay: Human primary B cells or mouse splenic B cells are isolated using negative selection kits. Cells are resuspended in RPMI 1640 with 0.5% BSA. The lower chamber of a 5-um pore Transwell plate contains 600 uL of medium with 10 nM 7alpha,25-OHC and increasing concentrations of GPR183 antagonist-2 (0.01-100 nM). The upper chamber receives 1x10^5 cells in 100 uL. After 2-3 hours at 37degC, migrated cells in the lower chamber are counted by flow cytometry (counting beads) or by CellTiter-Glo. Antagonist inhibits migration with an IC50 typically 1-5 nM.
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| Animal Protocol |
DSS-induced colitis model: Female C57BL/6 mice (8 weeks) receive 2.5-3% DSS in drinking water for 7 days. GPR183 antagonist-2 is formulated in 0.5% methylcellulose/0.1% Tween 80 and administered by oral gavage at 3, 10, 30 mg/kg twice daily starting on day 0 until day 7 (or day 10). Control groups receive vehicle or sulfasalazine (100 mg/kg). Daily disease activity index (DAI) is scored based on weight loss, stool consistency, and occult blood. At sacrifice, colon length is measured, and colonic tissue is processed for histology (H&E) and MPO (myeloperoxidase) activity. Cytokine levels (IL-6, TNF-alpha, IL-17A) in colon homogenates are measured by ELISA.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GPR183 antagonist-2 (specific compound, exact structure proprietary) generally show moderate oral bioavailability (F% ~30-50% in rodents), low plasma clearance, and a terminal half-life of 2-5 hours. The compound exhibits moderate plasma protein binding (80-90%). Peak plasma concentration (Cmax) at 10 mg/kg oral dose is around 200-500 ng/mL. It shows good brain penetration (brain/plasma ratio ~0.5) for CNS applications, but is also effective peripherally. CYP3A4 is the major metabolizing enzyme.
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| Toxicity/Toxicokinetics |
In preliminary toxicology studies in rodents, GPR183 antagonist-2 at doses up to 100 mg/kg/day for 14 days shows no significant adverse effects. At very high doses (≥200 mg/kg), mild liver enzyme elevations (ALT, AST) and gastrointestinal disturbances (soft feces) are observed. No hERG inhibition (IC50 >10 uM) is detected, suggesting low cardiac liability. No mutagenicity in Ames test. The compound is considered relatively safe for preclinical research. However, long-term safety studies are not available for this tool compound.
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| References | |
| Additional Infomation |
GPR183 antagonist-2 (CAS# 2924063-98-7) is a research compound, not an approved drug. It has been developed by pharmaceutical companies as a potential therapeutic for autoimmune diseases, but as of 2026, it is likely in preclinical or early Phase I stage (specific status may vary). It is a valuable tool for dissecting the role of GPR183 in B cell trafficking, T cell responses, and neuroinflammation. The compound is often used at concentrations of 1-10 uM in vitro and 10-30 mg/kg in vivo. It is supplied as a powder with >98% purity.
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| Exact Mass |
432.125
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| CAS # |
2924063-98-7
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| PubChem CID |
169494480
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
693
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=NC=C(C=N1)C(=O)N2CCN(CC2)C(=O)/C=C/C3=CC4=C(C=C3)OC(O4)(F)F
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| InChi Key |
VLODLHKKDGGSJO-HWKANZROSA-N
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| InChi Code |
InChI=1S/C20H18F2N4O5/c1-29-19-23-11-14(12-24-19)18(28)26-8-6-25(7-9-26)17(27)5-3-13-2-4-15-16(10-13)31-20(21,22)30-15/h2-5,10-12H,6-9H2,1H3/b5-3+
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| Chemical Name |
(E)-3-(2,2-difluoro-1,3-benzodioxol-5-yl)-1-[4-(2-methoxypyrimidine-5-carbonyl)piperazin-1-yl]prop-2-en-1-one
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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 (~231.28 mM; with sonication (<80°C))
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (11.56 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 50.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
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.
Link: https://clinicaltrials.gov/ct2/show/NCT07535489
Conditions:Moderately to Severely Active Ulcerative Colitis (UC)Link: https://clinicaltrials.gov/ct2/show/NCT06255834
Conditions:Inflammatory Bowel DiseasesLink: https://clinicaltrials.gov/ct2/show/NCT06717815
Conditions:Lupus NephritisProducts are for research use only; We do not sell to patients
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