AZD8797 - CX3CR1 Modulator - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAZD8797Cat. No.: HY-13848CAS No.: 911715-90-7分式: CHNOS分量: 403.56作靶点: CXCR作通路: GPCR/G Protein; Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 150 mg/mL (371.69 mM)* m

2、eans soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4779 mL 12.3897 mL 24.7795 mL5 mM 0.4956 mL 2.4779 mL 4.9559 mL10 mM 0.2478 mL 1.2390 mL 2.4779 mL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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AZD8797竞争性、可服的 CX3CR1 变构调节剂，拮抗 CX3CR1 和 CXCR2

3、，Ki 分别为 3.9 和 2800nM。IC50 & Target 125I-CX3CL1-CX3CR1 125I-IL-8-CXCR23.9 nM (Ki, in HEK293S cells) 2800 nM (Ki, in HEK293S cells)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 In a flow adhesion assay, AZD8797 antagonizes the natural ligand, fractalkine (CX3CL1), in both humanwhole blood (hWB

4、) and in a B-lymphocyte cell line with IC50 values of 300 and 6 nM respectively. AZD8797also prevents G-protein activation in a 35SGTPS accumulation assay. AZD8797 positively modulates theCX3CL1 response at sub-micromolar concentrations in a -arrestin recruitment assay. In equilibriumsaturation bind

5、ing experiments, AZD8797 reduces the maximal binding of 125I-CX3CL1 without affecting Kd1. AZD8797 binds selectively with high affinity to human and rat CX3CR1 (Ki of hCX3CR1, 4 nM; Ki ofrCX3CR1, 7 nM, respectively). The equilibrium dissociation constant, KB, demonstrates that AZD8797 is avery poten

6、t inhibitor for human CX3CR1 (10 nM). The potency is threefold lower for rat CX3CR1 (29 nM) anddecreases even further at mouse CX3CR1 (54 nM) 2.体内研究 AZD8797 treatment in Dark Agouti rats with myelin oligodendrocyte glycoprotein-induced EAE results inreduced paralysis, CNS pathology, and incidence of

7、 relapses. The compound is effective when startingtreatment before onset, as well as after the acute phase 2.PROTOCOLKinase Assay 1 CHO-hCX3CR1 membranes together with different concentrations of AZD8797 are incubated in 50 mMHEPES, 100 mM NaCl, 5 mM MgCl2, 10 M GDP and 0.01% gelatin in a MicroWell

8、96-well plate. 0.56 Ci/mL 35SGTPS and EC80 of CX3CL1 are then added. The plate is incubated at 30C for 1 h andsubsequently unbound 35SGTPS is separated from bound by vacuum filtration to a Printed Filtermat B.The different AZD8797 concentrations are achieved by stepwise dilution in DMSO to achieve a

9、 final DMSOconcentration of 1% in all wells after addition of assay buffer, regardless of AZD8797 concentration 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: AZD8797 is formulated in 3035% (wt/wt) hydroxy-propyl-beta-cyklodextrin and ad

10、ministered s.c.Administration 2 through osmotic minipumps. Treatment is blinded to the operator. The plasma concentration of AZD8797 isanalyzed twice from each rat 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Cancer. 2018 Sep 8;9(19):

11、3603-3612.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Cederblad L, et al. AZD8797 is an allosteric non-competitive modulator of the human CX3CR1 receptor. Biochem J. 2016 Mar1;473(5):641-9.2. Ridderstad Wollberg A, et al. Pharmacological inhibition of the chemokine receptor

12、 CX3CR1 attenuates disease in a chronic-relapsingrat model for multiple sclerosis. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5409-14.3. Sofia Karlstro, et al. Substituted 7-amino-5-thio-thiazolo4,5-dpyrimidines as potent and selective antagonists of the fractalkine receptor(CX3CR1). J Med Chem. 2013 Apr 25;56(8):3177-90.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMcePdfHeightCautio