AZ1495|cas:2196204-23-4|西域试剂

AZ1495,98.18%

产品编号：Bellancom-111101| CAS NO：2196204-23-4| 分子式：C₂₁H₃₁N₅O₂| 分子量：385.50

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货号	价格	库存与货期
Bellancom-111101	￥3900.00	杭州北京（现货）
Bellancom-111101	￥5500.00	杭州北京（现货）
Bellancom-111101	￥7800.00	杭州北京（现货）
Bellancom-111101	￥11000.00	杭州北京（现货）

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AZ1495

产品介绍

AZ1495，一种弱碱，是一种有效的白细胞介素-1 受体相关激酶 4 (IRAK4) 抑制剂，具有口服活性。AZ1495 对 IRAK4 和 IRAK1 具有良好的理化和激酶选择性，其 IC₅₀ 值分别为 0.005 μM 和 0.023 μM。AZ1495 具有 IRAK4 抑制作用，K_d 值为 0.0007 μM。AZ1495 可用于弥漫大 B 细胞淋巴瘤 (DLBCL) 的研究。

生物活性

AZ1495, a weak base, is a potent orally active interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor. AZ1495 has a favorable physicochemical and kinase selectivity for IRAK4 and IRAK1 with IC₅₀ values of 0.005 μM and 0.023 μM, respectively. AZ1495 has IRAK4 inhibition with a K_d value of 0.0007 μM. AZ1495 can be used for the research of diffuse large B-cell lymphoma (DLBCL).

体外研究

AZ1495 (compound 28) (10 μM,1 h) has kinase selectivity for IRAK4 with IC₅₀ values of 0.005 μM (enzyme assay) and 0.052 μM (cellular assay), respectively.
AZ1495 (10 μM,1 h) has kinase inhibition for IRAK4 with an IC₅₀ value of 0.005 μM and K_d value of 0.0007 μM.
AZ1495 (0.001-100 μM, 72 h) inhibits NF-κB activation and growth of ABC-DLBCL cell lines in a dosedependent manner.
AZ1495 (0-3.3 μM, 14 h) completely inhibits NF-κB signaling and induces cell death at lower concentration in combination with a BTK inhibitor in OCI-LY10 cells.

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

Cell Viability Assay

Cell Line:	OCI-LY10 and SUDHL2 cells
Concentration:	0.001-100 μM
Incubation Time:	72 h
Result:	Inhibited growth of OCI-LY10 cells in a dosedependent manner, whereas SUDHL2, a GCB-cell line was not sensitive and no increased cell killing to IRAK4 inhibitor. Increased the cell death in OCI-LY10 cells upon increasing concentrations of compound 28 and BTK ibrutinib.

Western Blot Analysis

Cell Line:	OCI-LY10 cells
Concentration:	0-3.3 μM
Incubation Time:	14 h
Result:	Inhibited IκBα phosphorylation with dose-dependentence in OCI-LY10 cells. Showed induction of apoptosis combination with 10 nM ibrutinib by cleavage of caspase 3 in OCI-LY10 cells.

体内研究
(In Vivo)

AZ1495 (compound 28) (oral, daily, 12.5 mg/kg) leds to tumor regression combination with ibrutinib in an ABC-DLBCL mouse model (OCI-LY10 cells).
AZ1495 (iv., 2 mg/kg and oral, 5mg/kg) is characterized by high clearance (Cl) in rat (75 mL/min/kg) and moderate predictions based on hepatocyte data (Clint 15 μl/min/106 cells, predicted clearance 42 mL/min/kg) with low bioavailability consistent with a high first pass effect.
AZ1495 (iv., 1 mg/kg) has low the amount of active renal secretion occurring in the dog.

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

Animal Model:	CB.17 SCID mice
Dosage:	12.5 mg/kg
Administration:	oral, daily, 12.5 mg/kg
Result:	Had modest anti-tumor activity as single agents but a combination ofibrutinib led to tumor regression and is well tolerated.

Animal Model:

rat

Dosage:

2 mg/kg, 5mg/kg

Administration:

iv., 2 mg/kg and oral, 5mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

Animal Model:

dog

Dosage:

1 mg/kg

Administration:

iv., 1 mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

体内研究

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

Animal Model:	CB.17 SCID mice
Dosage:	12.5 mg/kg
Administration:	oral, daily, 12.5 mg/kg
Result:	Had modest anti-tumor activity as single agents but a combination ofibrutinib led to tumor regression and is well tolerated.

Animal Model:

rat

Dosage:

2 mg/kg, 5mg/kg

Administration:

iv., 2 mg/kg and oral, 5mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

Animal Model:

dog

Dosage:

1 mg/kg

Administration:

iv., 1 mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

体内研究

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

Animal Model:	CB.17 SCID mice
Dosage:	12.5 mg/kg
Administration:	oral, daily, 12.5 mg/kg
Result:	Had modest anti-tumor activity as single agents but a combination ofibrutinib led to tumor regression and is well tolerated.

Animal Model:

rat

Dosage:

2 mg/kg, 5mg/kg

Administration:

iv., 2 mg/kg and oral, 5mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

Animal Model:

dog

Dosage:

1 mg/kg

Administration:

iv., 1 mg/kg

Result:

Species	Dose (mg/kg)	Cl (mL/min/kg)	Vss(L/kg)	PO halflife (h)	IV halflife (h)	Fabs (%)	F (%)
Rat	2，5	75	2.1	2.0	0.8	100	28
Dog	1	29	3.0	-	3.3	-	-

性状

Solid

溶解性数据

In Vitro:

DMSO : 10 mg/mL (25.94 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.5940 mL	12.9702 mL	25.9403 mL
5 mM	0.5188 mL	2.5940 mL	5.1881 mL
10 mM	0.2594 mL	1.2970 mL	2.5940 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: ≥ 1 mg/mL (2.59 mM); Clear solution

此方案可获得 ≥ 1 mg/mL (2.59 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 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: ≥ 1 mg/mL (2.59 mM); Clear solution

此方案可获得 ≥ 1 mg/mL (2.59 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 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: ≥ 1 mg/mL (2.59 mM); Clear solution

此方案可获得 ≥ 1 mg/mL (2.59 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 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。