| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
(R)-SCH 546738 targets the CXCR3 chemokine receptor (G protein-coupled receptor family) [8L6-L7, L9-L10, L16-L17]. It is a non-competitive antagonist of human CXCR3, meaning it binds to a site distinct from the orthosteric (chemokine) binding pocket to inhibit receptor activation. The compound exhibits high affinity for the human CXCR3 receptor, with a Ki (inhibition constant) value of 0.4 nM [8L6-L7, L9-L11, L19-L20, L23-L25].
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| ln Vitro |
(R)-SCH 546738 is the active R-enantiomer of SCH 546738. As a potent CXCR3 antagonist with a Ki of 0.4 nM for the human receptor, it effectively blocks CXCR3-mediated signaling in vitro. This inhibition prevents chemokine (CXCL9, CXCL10, CXCL11)-induced chemotaxis, calcium flux, and other downstream signaling events in CXCR3-expressing immune cells, such as activated T cells, Th1 cells, and natural killer (NK) cells. The compound demonstrates high selectivity for CXCR3 over other chemokine receptors.
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| ln Vivo |
(R)-SCH 546738 is orally active, making it suitable for in vivo studies. SCH 546738 (the racemate or parent compound) has been shown to effectively block CXCR3-mediated immune cell recruitment in various animal models of inflammation and autoimmunity, including psoriasis, rheumatoid arthritis, and multiple sclerosis models. By blocking CXCR3, these antagonists reduce the infiltration of Th1 cells into inflamed tissues, leading to decreased disease severity. The R-isomer is presumed to retain or exceed this in vivo activity.
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| Enzyme Assay |
Non-competitive CXCR3 binding can be assessed using a radioligand binding assay with membranes from cells expressing human CXCR3. Procedure: Prepare membrane fractions from CXCR3-expressing HEK-293 cells. Incubate membranes with 0.1 nM [125I]-CXCL10 (or another labeled chemokine) and varying concentrations of (R)-SCH 546738 (e.g., 0.001 nM to 10 microM) in binding buffer for 2-4 hours at room temperature. Bound ligand is separated by rapid filtration through GF/B glass fiber filters. Radioactivity is measured in a scintillation counter. For non-competitive antagonism, a Schild analysis is performed to determine the binding mode.
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| Cell Assay |
A CXCR3-mediated chemotaxis assay is used to evaluate functional antagonism. Procedure: Primary human CD4+ T cells or CXCR3-transfected cells are isolated and labeled with a fluorescent dye (e.g., Calcein-AM). Cells are resuspended in serum-free medium containing varying concentrations of (R)-SCH 546738 (e.g., 0.01, 0.1, 1, 10, 100 nM) and added to the upper chamber of a 96-well Transwell plate (5-microm pore size). The lower chamber contains the chemokine CXCL10 (10-100 ng/mL). The plate is incubated at 37degC for 2-4 hours to allow cell migration. Migrated cells in the lower chamber are then quantified by measuring fluorescence. The IC50 for inhibition of chemotaxis is calculated.
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| Animal Protocol |
Mouse model of CXCR3-driven inflammation (e.g., psoriasis-like inflammation): Female C57BL/6 mice are injected intradermally with CXCL10 in the ear (20 ng/ear) or imiquimod cream is applied to induce psoriasis-like skin inflammation. (R)-SCH 546738 is administered orally at doses of 1-10 mg/kg daily for 7-14 days. Ear thickness is measured daily as a readout of inflammation. At study endpoint, ears or skin sections are harvested for histological analysis (H&E staining to measure epidermal thickness, CD8+ or CD4+ T cell infiltration by immunohistochemistry). Cytokine levels in tissue homogenates (IFN-gamma, CXCL10) are quantified by ELISA.
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| ADME/Pharmacokinetics |
As an orally active small molecule, (R)-SCH 546738 is designed for oral administration. SCH 546738, the parent compound, has been characterized with favorable PK properties, including good oral bioavailability (e.g., >50%), moderate half-life (t1/2 of 2-8 hours), and sufficient plasma exposure to achieve pharmacological activity. Based on its potent in vitro activity (Ki = 0.4 nM), low nanomolar concentrations are expected to be sufficient for in vivo receptor occupancy, which is achievable with standard oral dosing in preclinical species.
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| Toxicity/Toxicokinetics |
Specific toxicological data for (R)-SCH 546738 is not available in the search results. As a CXCR3 antagonist, potential toxicities may be related to modulation of the immune system. Given that CXCR3 is involved in Th1-type immune responses, chronic antagonism could increase susceptibility to certain pathogens or affect normal immune surveillance. The non-competitive mode of action may have implications for safety, such as potential for off-target GPCR interactions. A full toxicology evaluation would be required before clinical development.
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| References | |
| Additional Infomation |
(R)-SCH 546738 is the R-enantiomer of the potent CXCR3 antagonist SCH 546738 [8L6-L7, L8-L10]. CXCR3 is a chemokine receptor that directs the migration of activated T cells (particularly Th1 cells) to sites of inflammation in a range of autoimmune and inflammatory diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and allograft rejection. Therefore, CXCR3 antagonists like (R)-SCH 546738 have been actively pursued as potential oral therapies for these conditions. This research-use compound may serve as a valuable tool for investigating the role of CXCR3 in disease models and for developing new immunomodulatory therapies. The exact Ki value for the R-isomer is not specifically provided, but the parent compound SCH 546738 has a Ki of 0.4 nM for human CXCR3 [8L6-L7].
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| Molecular Formula |
C23H31CL2N7O
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|---|---|
| Molecular Weight |
492.44
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| Exact Mass |
491.197
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| CAS # |
2181148-54-7
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| PubChem CID |
98005897
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.326±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
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| Boiling Point |
628.2±55.0 °C(predicted)
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| LogP |
0
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
642
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC[C@@H]1CN(CCN1C2CCN(CC2)CC3=CC=C(C=C3)Cl)C4=NC(=C(N=C4Cl)C(=O)N)N
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| InChi Key |
UYDYJFWSPRQEAX-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C23H31Cl2N7O/c1-2-17-14-31(23-20(25)28-19(22(27)33)21(26)29-23)11-12-32(17)18-7-9-30(10-8-18)13-15-3-5-16(24)6-4-15/h3-6,17-18H,2,7-14H2,1H3,(H2,26,29)(H2,27,33)/t17-/m1/s1
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| Chemical Name |
3-amino-6-chloro-5-[(3R)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyrazine-2-carboxamide
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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 : ~12.5 mg/mL (~25.38 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0307 mL | 10.1535 mL | 20.3070 mL | |
| 5 mM | 0.4061 mL | 2.0307 mL | 4.0614 mL | |
| 10 mM | 0.2031 mL | 1.0154 mL | 2.0307 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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