AZ084

Product NameAZ084
CAS929300-19-6
MFC26H34N4O2
MW434.57
EINECS
MOL File929300-19-6.mol

Chemical Properties

Boiling point	636.0±55.0 °C(Predicted)
Density	1.24±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : 250 mg/mL (575.28 mM; Need ultrasonic)
form	Solid
pka	9.20±0.20(Predicted)
color	Light yellow to yellow

Usage And Synthesis

Uses

AZ084 is a potent, selective, allosteric and oral active CCR8 allosteric antagonist, with a Ki of 0.9 nM. Has potential to treat asthma[1]. AZ084 restrains the formation of the immunologically tolerant pre-metastatic niche (PMN) and tumor cells metastasis in lung by downregulating Treg differentiation. AZ084 can be used in studies of asthma and cancer[1][2].

in vivo

AZ084 (5 mg/kg; i.p.; every third day for 9 or 21 days) restrains the formation of the immunologically tolerant PMN and tumor cells metastasis in lung by downregulating Treg differentiation^[1].
AZ084 (434.57-869.14 mg/kg; i.v.; single) shows a bioavailability >70% in rats^[2].

Animal Model:	C57BL/6 J mice (subcutaneous LLC tumor model)^[1].
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^[2].

Dosage:

434.57-869.14 mg/kg (in 0.9% NaCl)

Administration:

Intravenous injection, single.

Result:

1.19Pharmacokinetic Parameters of AZ084 in Female Balb/C mice, male Wistar rats and female Beagle dogs^[2].

	IV (434.57-869.14 mg/kg)
Dog plasma protein binding (% free)	45.7
Mu plasma protein binding (% free)	55.6
Hu plasma protein binding (% free)	31.0
Rat plasma protein binding (% free)	47.0
Rat HW plasma PK CL (mL/min/kg)	15.0
Rat HW plasma PK V_ss (L/kg)	6.0
Rat HW plasma PK T_1/2 (h)	5.4
Rat HW plasma PK C_max (μM)	0.5
Rat HW plasma PK bioavailability (%)	68.0

IC 50

CCR8: 0.9 nM (Ki)

References

[1] Wang M, et al. Tumor-derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1+ fibroblast and CCR8+ Treg cell interactions. Cancer Immunol Immunother. 2022 Apr 15. DOI:10.1007/s00262-022-03196-3
[2] Connolly S, et al. Orally bioavailable allosteric CCR8 antagonists inhibit dendritic cell, T cell and eosinophil migration. Biochem Pharmacol. 2012 Mar 15;83(6):778-87. DOI:10.1016/j.bcp.2011.12.021

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