AZ084|cas:929300-19-6|西域试剂

AZ084,99.69%

产品编号：Bellancom-119217| CAS NO：929300-19-6| 分子式：C₂₆H₃₄N₄O₂| 分子量：434.57

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-119217	￥3100.00	杭州北京（现货）
Bellancom-119217	￥4650.00	杭州北京（现货）
Bellancom-119217	￥14000.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

AZ084

产品介绍

AZ084 是一种具有口服活性的选择性 CCR8 的变构拮抗剂，其K_i 值为 0.9 nM。AZ084 可通过下调 Treg 的分化来抑制免疫耐受性 PMN 的形成和肿瘤细胞在肺部的转移。AZ084 可用于哮喘和癌症的研究。

生物活性

AZ084 is a potent, selective, allosteric and oral active CCR8 allosteric antagonist, with a K_i of 0.9 nM. Has potential to treat asthma. 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.

体外研究

AZ084 (5 μg/mL; single daily for 4 days) suppresses proportion of Tregs and reduces T cells that expresses CCR8 (co-cultured in vitro with LLC-exo MPF CM).
AZ084 (0-10 µM) inhibits AML, DC and T cells with IC₅₀s of 1.3, 4.6 and 5.7 nM, respectively.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究
(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.
AZ084 (434.57-869.14 mg/kg; i.v.; single) shows a bioavailability >70% in rats.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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:

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

	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

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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:

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

	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

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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:

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

	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

性状

Solid

溶解性数据

In Vitro:

DMSO : 250 mg/mL (575.28 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3011 mL	11.5056 mL	23.0113 mL
5 mM	0.4602 mL	2.3011 mL	4.6023 mL
10 mM	0.2301 mL	1.1506 mL	2.3011 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (4.79 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.79 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (4.79 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.79 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.79 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.79 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。