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
SCH 527123是一种强效、选择性的CXCR1和CXCR2受体拮抗剂，对小鼠（Kd=0.20nM）、大鼠（Kd=0.20nM）和食蟹猴（Kd=0.08nM）的CXCR2受体具有高亲和力。
Cas No.:473727-83-2
Sample solution is provided at 25 µL, 10mM.
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SCH 527123 is a potent, selective antagonist of the CXCR1 and CXCR2 receptors with high affinity to the CXCR2 receptors of mouse (Kd=0.20nM), rat (Kd=0.20nM), and cynomolgus monkey (Kd=0.08nM) [1]. SCH 527123 can inhibit tumor growth, microvessel density and CXCR2-mediated signal transduction by reducing the phosphorylation levels of the NF-κB/MAPK/AKT pathway[2]. SCH 527123 has been widely used to inhibit the growth, angiogenesis and metastasis of malignant melanoma[3].
In vitro, SCH 527123 treatment for 72h significantly inhibited the proliferation of Caco2 cells and HCT116 cells, with IC50 values of 18.78μM and 28.95μM, respectively[4]. 80μM of SCH 527123 pretreatment for 4 hours significantly inhibited the proliferation of AsPC-1 cells stimulated by 25ng/ml of IL-8[5].
In vivo, SCH 527123 treatment via oral administration at a dose of 100mg/kg/day for 21 consecutive days inhibits tumor growth in a A375SM cell-xenograft mouse model and reduce the density of tumor microvessels[6]. Oral administration of SCH 527123 (3mg/kg) 2 hours before and 4 hours after lipopolysaccharide challenge suppresses pulmonary neutrophilia and goblet cell hyperplasia in mice[7]. Twice-daily oral administration of SCH 527123 at a dose of 10mg/kg for 21 consecutive days inhibited leukocyte migration into the lungs and reversed pulmonary arterial hypertension in L1Cre(+);Bmpr2f/f mice[8].
References:
[1] Chapman R W, Minnicozzi M, Celly C S, 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]. The Journal of pharmacology and experimental therapeutics, 2007, 322(2): 486-493.
[2] Xu X, Xia J, Wang X. Potential anticancer therapies via CXCL5 and its receptors[J]. Expert Review of Clinical Pharmacology, 2012, 5(4): 347-350.
[3] Sharma B, Singh S, Varney M L, et al. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma[J]. Expert opinion on therapeutic targets, 2010, 14(4): 435-442.
[4] Ning Y, Labonte M J, Zhang W, et al. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models[J]. Molecular cancer therapeutics, 2012, 11(6): 1353-1364.
[5] Fu S, Chen X, Lin H J, et al. Inhibition of interleukin 8/C‑XC chemokine receptor 1,/2 signaling reduces malignant features in human pancreatic cancer cells[J]. International Journal of Oncology, 2018, 53(1): 349-357.
[6] Singh S, Sadanandam A, Nannuru K C, et al. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis[J]. Clinical Cancer Research, 2009, 15(7): 2380-2386.
[7] Chapman R W, Minnicozzi M, Celly C S, 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]. The Journal of pharmacology and experimental therapeutics, 2007, 322(2): 486-493.
[8] Burton V J, Holmes A M, Ciuclan L I, et al. Attenuation of leukocyte recruitment via CXCR1/2 inhibition stops the progression of PAH in mice with genetic ablation of endothelial BMPR-II[J]. Blood, The Journal of the American Society of Hematology, 2011, 118(17): 4750-4758.
SCH 527123是一种强效、选择性的CXCR1和CXCR2受体拮抗剂，对小鼠（Kd=0.20nM）、大鼠（Kd=0.20nM）和食蟹猴（Kd=0.08nM）的CXCR2受体具有高亲和力[1]。SCH 527123可通过降低NF-κB/MAPK/AKT通路的磷酸化水平，抑制肿瘤生长、微血管密度和CXCR2介导的信号转导[2]。SCH 527123已广泛应用于抑制恶性黑色素瘤的生长、血管生成和转移[3]。
在体外，SCH 527123处理72小时显著抑制了Caco2细胞和HCT116细胞的增殖，IC50值分别为18.78μM 和28.95μM[4]。用80μM的SCH 527123预处理4小时显著抑制了由25ng/ml的IL-8刺激AsPC-1细胞增殖[5]。
在体内，以100mg/kg/day的剂量连续21天口服SCH 527123，可抑制A375SM细胞异种移植小鼠模型的肿瘤生长并降低肿瘤微血管密度[6]。在脂多糖刺激前2小时和刺激后4小时分别口服SCH 527123（3mg/kg）可抑制小鼠肺部中性粒细胞增多和杯状细胞增生[7]。每日两次口服10mg/kg剂量的SCH 527123，连续21天，可抑制白细胞向肺部迁移，并逆转L1Cre(+);Bmpr2f/f小鼠的肺动脉高压[8]。
| Cell experiment [1]: | |
Cell lines | AsPC-1 cells |
Preparation Method | AsPC-1 cells were seeded at a density of 3000 cells per well in a 96-well microplate and cultured in 100μl DMEM medium containing 10% FBS at 37°C overnight. The next day, when the cell confluence reached approximately 20%, the medium in each well was replaced, 100μl DMEM+10% FBS was added, and different concentrations of SCH 527123 (20, 40, 60, 80, and 100μM) or DMSO solvent control were added. All treatments were carried out under the same conditions (DMEM+10% FBS). After 72 hours of culture, 25μl MTT solution was added to each well, and the cells were further cultured for 4 hours. Then, DMF dissolution solution (150μl) was added to dissolve the methylene blue crystals, and the cells were placed in a sealed humidified incubator, protected from light, and incubated at room temperature overnight. The absorbance at 595nm was measured. |
Reaction Conditions | 20, 40, 60, 80, and 100μM; 72h |
Applications | SCH 527123 treatment inhibited the viability of AsPC-1 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male C57Bl/6 Balb/c mice |
Preparation Method | Male C57Bl/6 Balb/c mice were raised in a standard sterile environment and had free access to food and water. Subcutaneous implants of HCT116 xenograft tumors were made in the mice and allowed to grow to approximately 100mm3 (Day 0). The animals were randomly divided into 3 groups: the control group, the SCH 527123 group, and the oxaliplatin group. SCH 527123 was administered by gavage at a dose of 50mg/kg once daily, and oxaliplatin was injected intraperitoneally at a dose of 7.5mg/kg every 4 days for 21 days. The tumor size was recorded daily, and the microvessel density of the tumor samples was quantified on the last day. |
Dosage form | 50mg/kg/day for 21 days; p.o. |
Applications | SCH 527123 treatment significantly decreased tumor growth and microvessel density in mice. |
References: | |
| 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 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5162 mL | 12.5811 mL | 25.1623 mL |
| 5 mM | 503.2 μL | 2.5162 mL | 5.0325 mL |
| 10 mM | 251.6 μL | 1.2581 mL | 2.5162 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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- Purity: >99.00%
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