AZD8797_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries
https://www.sodocs.net/doc/5c14477964.html, Data Sheet
BIOLOGICAL ACTIVITY:
AZD8797 is an allosteric non–competitive modulator of the human CX3CR1 receptor; antagonizes CX3CL1 with IC 50 values of 6 and 300 nM in B–lymphocyte cell line and human whole blood, respectively.
IC50 & Target: IC50: 6 nM (CX3CL1); 300 nM (CX3CL1)[1]
In Vitro: In a flow adhesion assay, AZD8797 antagonizes the natural ligand, fractalkine (CX3CL1), in both human whole blood (hWB)and in a B–lymphocyte cell line with IC 50 values of 300 and 6 nM respectively. AZD8797 also prevents G–protein activation in a [35S]GTPγS accumulation assay. AZD8797 positively modulates the CX3CL1 response at sub–micromolar concentrations in a
β–arrestin recruitment assay. In equilibrium saturation binding experiments, AZD8797 reduces the maximal binding of 125I–CX3CL1 without affecting K d [1]. AZD8797 binds selectively with high affinity to human and rat CX3CR1 (K i of hCX3CR1, 4 nM; K i of rCX3CR1, 7 nM, respectively). The equilibrium dissociation constant, K B , demonstrates that AZD8797 is a very potent inhibitor for human CX3CR1 (10 nM). The potency is threefold lower for rat CX3CR1 (29 nM) and decreases even further at mouse CX3CR1 (54nM)[2].
In Vivo: AZD8797 treatment in Dark Agouti rats with myelin oligodendrocyte glycoprotein–induced EAE results in reduced paralysis,CNS pathology, and incidence of relapses. The compound is effective when starting treatment before onset, as well as after the acute phase [2].
PROTOCOL (Extracted from published papers and Only for reference)
Kinase Assay:[1]CHO–hCX3CR1 membranes together with different concentrations of AZD8797 are incubated in 50 mM HEPES, 100mM NaCl, 5 mM MgCl 2, 10 μM GDP and 0.01% gelatin in a MicroWell 96–well plate. 0.56 μCi/mL [35S]GTPγS and EC 80 of
CX3CL1 are then added. The plate is incubated at 30°C for 1 h and subsequently unbound [35S]GTPγS 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 final DMSO concentration of 1% in all wells after addition of assay buffer, regardless of AZD8797 concentration [1].
Animal Administration:[2]Rat: AZD8797 is formulated in 30–35% (wt/wt) hydroxy–propyl–beta–cyklodextrin and administered s.c.through osmotic minipumps. Treatment is blinded to the operator. The plasma concentration of AZD8797 is analyzed twice from each rat [2].
References:
[1]. Cederblad L, et al. AZD8797 is an allosteric non–competitive modulator of the human CX3CR1 receptor. Biochem J. 2016 Mar 1;473(5):641–9.
[2]. Ridderstad Wollberg A, et al. Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic–relapsing rat model for multiple sclerosis. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5409–14.
Product Name:
AZD8797Cat. No.:
HY-13848CAS No.:
911715-90-7Molecular Formula:
C 19H 25N 5OS 2Molecular Weight:
403.56Target:
CXCR; CXCR Pathway:
GPCR/G Protein; Immunology/Inflammation Solubility:
DMSO: ≥ 150 mg/mL
Caution: Product has not been fully validated for medical applications. For research use only.
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