SCH 527123
(Synonyms: 3-[[3-[(二甲基氨基)羰基]-2-羟基苯基]氨基]-4-[[(R)-1-(5-甲基呋喃-2-基)丙基]氨基]-3-环丁烯-1,2-二酮,SCH-527123;SCH527123) 目录号 : GC16100
An allosteric antagonist of CXCR1 and CXCR2
Cas No.:473727-83-2
Sample solution is provided at 25 µL, 10mM.
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SCH-527123 is a novel, selective CXC chemokine receptor 2 (CXCR2) antagonist.
SCH-527123 was able to suppress CXCR2-mediated signal transduction as shown through decreased phosphorylation of the NF-κB/mitogen-activated protein kinase (MAPK)/AKT pathway [1].
Cells were treated with increasing concentrations of SCH-527123 for 72 hours and showed dose-dependent growth inhibitory activity with IC50 (72 h) values ranging from 18 to 40 μmol/L. Importantly the IL-8–overexpressing cells showed a higher IC50 (72 h) concentration of SCH-527123 than parental cells [HCT116 and E2 (P < 0.005): 28.9 ± 0.02 μmol/L and 39.5 ± 0.01 μmol/L, respectively; Caco2 and IIIe (P < 0.005): 18.8 ± 0.03 μmol/L and 25.5 ± 0.02 μmol/L, respectively]. Therefore, SCH-527123 decreased growth inhibitory activity in colorectal cancer cell lines [2].
References
References:
[1]. Holz O, Khalilieh S, Ludwig-Sengpiel A et al. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Holz O1, Khalilieh S, Ludwig-Sengpiel A et al.
[2]. Holz O1, Khalilieh S, Ludwig-Sengpiel A et al. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther. 2012 Jun;11(6):1353-64.
| Cell experiment[1]: | |
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Cell lines |
Human melanoma cell line (A375SM ) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μg/ml, 72h |
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Applications |
SCH-479833 or SCH 527123 inhibited the melanoma cell proliferation, chemotaxis, and invasive potentialin vitro.Treatment of melanoma cells with SCH-479833 or SCH 527123 also inhibited tumor growth. Histologic and histochemical analyses showed significant (P<0.05) decreases in tumor cell proliferation and microvessel density in tumors. Moreover, we observed a significant increase in melanoma cell apoptosis in SCH-479833- or SCH 527123-treated animals compared with controls. |
| Animal experiment[1]: | |
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Animal models |
Male BALB/c mice, 20-25 g |
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Dosage form |
Sch-527123 was suspended in 0.4% methylcellulose |
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Applications |
Sch 527123 was bound with high affinity to the CXCR2 receptors of mouse (Kd=0.20 nM), rat (Kd=0.20 nM), and cynomolgus monkey (Kd=0.08 nM) and was a potent antagonist of CXCR2-mediated chemotaxis (IC50~3– 6 nM). In contrast, Sch 527123 bound to cynomolgus CXCR1 with lesser affinity (Kd=41 nM) and weakly inhibited cynomolgus CXCR1-mediated chemotaxis (IC50 ~1000 nM). Oral treatment with Sch-527123 blocked pulmonary neutrophilia (ED50=1.2 mg/kg) and goblet cell hyperplasia (32–38% inhibition at 1–3 mg/kg) in mice following the intranasal lipopolysaccharide (LPS) administration. In rats, Sch-527123 suppressed the pulmonary neutrophilia (ED=501.8 mg/kg) and increase in bronchoalveolar lavage (BAL) mucin content (ED 50≤ 0.1 mg/kg) induced by intratracheal (i.t.) LPS. Sch-527123 also suppressed the pulmonary neutrophilia (ED50=1.3 mg/kg), goblet cell hyperplasia (ED 50=0.7 mg/kg), and increase in BAL mucin content (ED50<1 mg/kg) in rats after i.t. administration of vanadium pentoxide. In cynomolgus monkeys, Sch-527123 reduced the pulmonary neutrophilia induced by repeat bronchoscopy and lavage (ED50=0.3 mg/kg). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Singh S1, Sadanandam A, Nannuru KC et al. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis. Clin Cancer Res. 2009 Apr 1;15(7):2380-6. 2. Chapman RW1, Minnicozzi M, Celly CS et al. A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther. 2007 Aug;322(2):486-93. Epub 2007 May 11. | |
| Cas No. | 473727-83-2 | SDF | |
| 别名 | 3-[[3-[(二甲基氨基)羰基]-2-羟基苯基]氨基]-4-[[(R)-1-(5-甲基呋喃-2-基)丙基]氨基]-3-环丁烯-1,2-二酮,SCH-527123;SCH527123 | ||
| 化学名 | 2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide | ||
| Canonical SMILES | CCC(C1=CC=C(O1)C)NC2=C(C(=O)C2=O)NC3=CC=CC(=C3O)C(=O)N(C)C | ||
| 分子式 | C21H23N3O5 | 分子量 | 397.42 |
| 溶解度 | ≥ 19.85 mg/mL in DMSO, ≥ 103 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5162 mL | 12.5811 mL | 25.1623 mL |
| 5 mM | 0.5032 mL | 2.5162 mL | 5.0325 mL |
| 10 mM | 0.2516 mL | 1.2581 mL | 2.5162 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet