911715-90-7
911715-90-7 structure
- Name: AZD8797
- Chemical Name: AZD8797
- CAS Number: 911715-90-7
- Molecular Formula: C19H25N5OS2
- Molecular Weight: 403.565
- Catalog: Signaling Pathways GPCR/G Protein CXCR
- Create Date: 2018-06-02 17:09:41
- Modify Date: 2024-01-09 08:25:09
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AZD8797 is an allosteric non-competitive modulator of the human CX3CR1 receptor; antagonizes CX3CR1 and CXCR2 with Kis of 3.9 and 2800 nM, respectively.
| Name | AZD8797 |
|---|---|
| Synonyms |
(2R)-2-[(2-Amino-5-{[(1S)-1-phenylethyl]sulfanyl}[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methyl-1-pentanol
1-Pentanol, 2-[[2-amino-5-[[(1S)-1-phenylethyl]thio]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methyl-, (2R)- |
| Description | AZD8797 is an allosteric non-competitive modulator of the human CX3CR1 receptor; antagonizes CX3CR1 and CXCR2 with Kis of 3.9 and 2800 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
[125I]-CX3CL1-CX3CR1:3.9 nM (Ki, in HEK293S cells) 125I-IL-8-CXCR2:2800 nM (Ki, in HEK293S cells) |
| 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 IC50 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 Kd[1]. AZD8797 binds selectively with high affinity to human and rat CX3CR1 (Ki of hCX3CR1, 4 nM; Ki of rCX3CR1, 7 nM, respectively). The equilibrium dissociation constant, KB, 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 (54 nM)[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]. |
| Kinase Assay | CHO-hCX3CR1 membranes together with different concentrations of AZD8797 are incubated in 50 mM HEPES, 100 mM NaCl, 5 mM MgCl2, 10 μM GDP and 0.01% gelatin in a MicroWell 96-well plate. 0.56 μCi/mL [35S]GTPγS and EC80 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 Admin | Rats: 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 |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 651.1±65.0 °C at 760 mmHg |
| Molecular Formula | C19H25N5OS2 |
| Molecular Weight | 403.565 |
| Flash Point | 347.6±34.3 °C |
| Exact Mass | 403.150055 |
| LogP | 4.60 |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.669 |
| Storage condition | 2-8℃ |