AZ084

Research use only, not for human use.

AZ084 (AZ-084) is a potent, selective, allosteric, orally available CCR8 antagonist with Ki of 0.9 nM.

AZ084 (AZ-084) is a potent, selective, allosteric, orally available CCR8 antagonist with Ki of 0.9 nM; demonstrates excellent selectivity in a panel of 141 kinases and receptors, also shows no binding activity at 10 uM towards any of the other chemokine receptors; demonstrates excellent selectivity, high metabolic stability in vitro and an attractive in vivo PK profile with a long half-life in rats; inhibits dendritic cell, T cell and eosinophil migration.

Cell Viability Assay Cell Line:Splenic T cells Concentration:5 μg/mL (single daily)Incubation Time:4 days Result:Reversed the increased proportion of Tregs among the CD4+ T cells co-cultured in vitro with LLC-exo MPF CM. Reduced T cells that expressed CCR8 (cultured in vitro with by LLC-exo MPF CM).Cell Viability Assay Cell Line:AML, DC and T cells Concentration:0-10 μM Incubation Time:Result:Showed high potency with pronounced dose-response dependent inhibition of chemotaxis with an IC50 of 1.3 nM in AML cells.

Animal Model:C57BL/6 J mice (subcutaneous LLC tumor model).Dosage:5 mg/kg Administration:Intraperitoneal injection, every third day for 9 or 21 days.Result:Inhibited Treg differentiation and tumor cell colonization of the lungs and reduced the number of CD4+Foxp3+ Tregs in the lungs of LLC-exo pre-injected mice (every third day for 9 days).Inhibited the LLC-exo-induced LLC cell seeding in lung and also significantly reduced Treg accumulation in LLC-exo stimulated mouse lungs(every third day for 21 days).Animal Model:Female Balb/C mice, male Wistar rats and female Beagle dogs.Dosage:434.57-869.14 mg/kg (in 0.9% NaCl) Administration: Intravenous injection, single.Result:Pharmacokinetic Parameters of AZ084 in Female Balb/C mice, male Wistar rats and female Beagle dogs.

AZ-084

GPCR/G Protein

Chemokine Receptor

Chemokine Receptor

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929300-19-6

434.584

C26H34N4O2

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (575.28 mM)

CC1(CC2=C(C=CC=C2O1)CN3CCC4(CC3)CCN(CC4)C(=O)C5=NC=C(C=C5)N)C

(5-aminopyridin-2-yl)(9-((2,2-dimethyl-2,3-dihydrobenzofuran-4-yl)methyl)-3,9-diazaspiro[5.5]undecan-3-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years