| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
(Rac)-SCH 563705 targets the chemokine receptors CXCR2 and CXCR1, which are G protein-coupled receptors (GPCRs) expressed on neutrophils and other immune cells. It acts as a dual antagonist, blocking both receptors simultaneously. For the active enantiomer SCH 563705, the IC50 values are 1.3 nM for CXCR2 and 7.3 nM for CXCR1, with Ki values of 1 nM and 3 nM, respectively. This blockade prevents neutrophil chemotaxis to sites of inflammation, reducing inflammatory damage in conditions such as arthritis.
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| ln Vitro |
Cells expressing human CXCR2 or CXCR1 are used. SCH 563705 effectively inhibits Gro-alpha and IL-8-induced human neutrophil migration (CXCR2 IC50 = 0.5 nM, CXCR1 IC50 = 37 nM). It also inhibits mouse CXCR2 (IC50 = 5.2 nM). No antagonist effect on Epac2 or protein kinase A activity is observed, indicating selectivity for CXCR chemokine receptors.
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| ln Vivo |
Oral administration of SCH 563705 (50 mg/kg) to BALB/c female mice decreases blood Ly6G+ Ly6C+ neutrophil frequency while leaving Ly6GLy6Chi monocyte levels unchanged. Treatment at 3-30 mg/kg p.o. causes a dose-dependent elevation in plasma levels of the CXCR2 ligand CXCL1, consistent with receptor blockade. In a mouse arthritis model, oral administration of SCH 563705 dose-dependently decreases paw thickness and reduces inflammation, bone, and cartilage degradation. SCH 563705 has favorable oral PK profiles in rats, mice, monkeys, and dogs.
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| Enzyme Assay |
Standard competitive radioligand binding assay using membranes expressing human CXCR1 or CXCR2. Membranes (5-20 microg protein) are incubated with 0.05-0.1 nM 125I-labeled IL-8 and varying concentrations of (Rac)-SCH 563705 (0.001 nM to 10 microM) in binding buffer (50 mM HEPES, 1 mM CaCl2, 5 mM MgCl2, 0.5% BSA, pH 7.4) for 1-2 hours at room temperature. Bound radioactivity is separated by filtration through GF/B filters. Non-specific binding is determined using 100-fold excess unlabeled IL-8. IC50 values are calculated, and Ki values are derived using the Cheng-Prusoff equation. For SCH 563705, this yielded Ki of 1 nM for CXCR2 and 3 nM for CXCR1.
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| Cell Assay |
Human peripheral blood neutrophils are isolated from whole blood using density gradient centrifugation. Cells are pre-treated with varying concentrations of (Rac)-SCH 563705 (0.001 nM to 1 microM) for 15-30 minutes. Chemotaxis is assessed in a 96-well Boyden chamber or transwell plate (3-5 microm pore size). The chemoattractant Gro-alpha (30 nM) or IL-8 (3 nM) is placed in the lower chamber, while pre-treated neutrophils are added to the upper chamber. After incubation at 37degC for 60-90 minutes, migrated cells in the lower chamber are quantified by Calcein-AM fluorescence. Inhibition of chemotaxis is expressed as percentage relative to vehicle control. IC50 values: CXCR2 0.5 nM, CXCR1 37 nM.
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| Animal Protocol |
Female BALB/c mice (6-8 weeks) are immunized intradermally with 50 microL of 2 mg/mL chick type II collagen emulsified in Freund's Complete Adjuvant, with a booster 21 days later. After arthritis onset (day 26-30), animals are randomized and treated orally with (Rac)-SCH 563705 at 3, 10, or 30 mg/kg once or twice daily for 7-14 days in 0.4% hydroxypropyl methyl cellulose vehicle. Disease progression is assessed daily by clinical scoring (0-4 per paw). Paw thickness is measured by calipers. At termination (day 35-42), blood and paw tissues are collected for histopathology (inflammation, pannus, bone erosion, cartilage degradation) and cytokine analysis.
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| ADME/Pharmacokinetics |
(Rac)-SCH 563705 has favorable oral pharmacokinetic profiles in rats, mice, monkeys, and dogs. SCH 563705 is dissolved in 0.4% hydroxypropyl methyl cellulose (HPMC) or a vehicle of 5% DMSO, 30% PEG300, 5% Tween 80, and 60% saline for in vivo studies. Following oral administration at 50 mg/kg in mice, target engagement is observed via reduction in neutrophil frequency. Powder should be stored at -20degC for up to 3 years, and in solvent at -80degC for up to 1 year. Specific half-life and Cmax values are not publicly available.
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| Toxicity/Toxicokinetics |
According to safety data for similar CXCR antagonists, the compound contains a pharmaceutically active ingredient and is harmful if swallowed. It may be irritating to skin, eyes, and respiratory tract. Handling requires appropriate personal protective equipment (gloves, lab coat, goggles) in a well-ventilated area. No formal toxicology studies (e.g., acute toxicity LD50, repeat-dose toxicity, genotoxicity, reproductive toxicity) have been published for (Rac)-SCH 563705 itself. However, the active enantiomer has been evaluated in multiple preclinical species at doses up to 50 mg/kg without reported mortality.
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| References |
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| Additional Infomation |
SCH 563705 was discovered at Schering-Plough Research Institute and reported in a 2007 SAR study (Chao J, et al. Bioorg Med Chem Lett. 2007;17(13):3778-83). The (S)-enantiomer is the more active form; the racemic mixture contains approximately 50% pharmacologically inactive enantiomer. (Rac)-SCH 563705 has been studied for acute respiratory syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, and other inflammatory conditions. The molecular mechanism involves blocking neutrophil recruitment to inflammation sites. No clinical trials or regulatory approvals exist.
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| Molecular Formula |
C23H27N3O5
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| Molecular Weight |
425.48
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| Exact Mass |
425.195
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| CAS # |
2701435-64-3
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| PubChem CID |
52911092
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
747
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC(C1=CC(=CO1)C(C)C)NC2=C(C(=O)C2=O)NC3=CC=CC(=C3O)C(=O)N(C)C
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| InChi Key |
DGKQQEVYYPCMNE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N3O5/c1-6-15(17-10-13(11-31-17)12(2)3)24-18-19(22(29)21(18)28)25-16-9-7-8-14(20(16)27)23(30)26(4)5/h7-12,15,24-25,27H,6H2,1-5H3
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| Chemical Name |
3-[[3,4-dioxo-2-[1-(4-propan-2-ylfuran-2-yl)propylamino]cyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide
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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 : ~200 mg/mL (~470.06 mM; with ultrasonication)
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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 | 2.3503 mL | 11.7514 mL | 23.5029 mL | |
| 5 mM | 0.4701 mL | 2.3503 mL | 4.7006 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3503 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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