您好,欢迎来到试剂仪器网! [登录] [免费注册]
试剂仪器网
位置:首页 > 产品库 > SCH 563705
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
SCH 563705
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SCH 563705图片
CAS NO:473728-58-4
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 425.49
Formula C23H27N3O5
CAS No. 473728-58-4
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 30 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES O=C(C(NC1=CC=CC(C(N(C)C)=O)=C1O)=C2N[C@H](CC)C3=CC(C(C)C)=CO3)C2=O
Synonyms SCH-563705; SCH 563705; SCH563705
实验参考方法
In Vitro

In vitro activity: SCH 563705 is a novel potent and orally active antagonist of CXCR2 and CXCR1 with good oral pharmacokinetic profiles in rat, mouse, monkey, and dog. It has IC50 values of 1.3 nM, 7.3 nM and Kis of 1 and 3 nM for CXCR2 and CXCR1, respectively. Targeting neutrophil migration with the CXCR2/CXCR1 antagonist SCH563705 led to a dose-dependent decrease in clinical disease scores and paw thickness measurements and clearly reduced inflammation and bone and cartilage degradation based on histopathology and paw cytokine analyses. In contrast, targeting monocyte migration with the CCR2 antagonist MK0812 had no effect on arthritis disease severity. The pharmacodynamic activities of both SCH563705 and MK0812 were verified by assessing their effects on the peripheral blood monocyte and neutrophil populations. SCH563705 selectively reduced the peripheral blood neutrophil frequency, and caused an elevation in the CXCR2 ligand CXCL1. MK0812 selectively reduced the peripheral blood monocyte frequency, and caused an elevation in the CCR2 ligand CCL2. The much greater impact of CXCR2/CXCR1 antagonism relative to CCR2 antagonism in this model of arthritis highlights the therapeutic potential for targeting CXCR2/CXCR1 in human arthritides.


Kinase Assay: SCH 563705 is a potent and orally available CXCR2 and CXCR1 antagonist, with IC50s of 1.3 nM, 7.3 nM and Kis of 1 and 3 nM, respectively. SCH 563705 shows potent inhibition against both Gro-a and IL-8 induced human neutrophil migration (chemotaxis IC50 = 0.5 nM, against 30 nM of Gro-a; chemotaxis IC50 = 37 nM, against 3 nM of IL-8). SCH 563705 potently inhibits mouse CXCR2 (IC50 = 5.2 nM)


Cell Assay: In contrast, targeting monocyte migration with the CCR2 antagonist MK0812 had no effect on arthritis disease severity. The pharmacodynamic activities of both SCH563705 and MK0812 were verified by assessing their effects on the peripheral blood monocyte and neutrophil populations. SCH563705 selectively reduced the peripheral blood neutrophil frequency, and caused an elevation in the CXCR2 ligand CXCL1. MK0812 selectively reduced the peripheral blood monocyte frequency, and caused an elevation in the CCR2 ligand CCL2. The much greater impact of CXCR2/CXCR1 antagonism relative to CCR2 antagonism in this model of arthritis highlights the therapeutic potential for targeting CXCR2/CXCR1 in human arthritides.

In VivoSCH 563705 has good oral pharmacokinetic profiles in rats, mice, monkeys and dogs. SCH 563705 (50 mg/kg p.o) reduces blood Ly6G+ Ly6C+neutrophil frequency and unchanged levels of Ly6GLy6Chi monocytes. SCH563705 (3-30 mg/kg p.o) treatment causes a dosedependent elevation in plasma levels of CXCL1
Animal model BALB/c mice with Anti-collagen antibody-induced arthritis model
Formulation & DosageSCH 563705 is dissolved in 0.4% METHOCEL E15 premium hydroxypropyl methylcellulose (MC); 30-50 mg/kg; p.o
References Biochem Biophys Res Commun. 2010 Jan 1;391(1):1080-6.