AZ-5104 is an active, demethylated metabolite of AZD 9291. AZ-5104 is an EGFR inhibitor with IC₅₀s of 1, 6, 1, 25 and 7 nM for EGFR^L858R/T790M, EGFR^L858R, EGFR^L861Q, EGFR and ErbB4, respectively.

AZ-5104 inhibits EGFR phosphorylation with IC₅₀s of 2, 1, 2, 53, and 33 nM in H1975 (EGFR^L858R/T790M), PC-9VanR (EGFR^{Exon 19 deletion/T790M}), PC-9 (EGFR^{Exon 19 deletion}), H2073 (WT), and LOVO (WT), respectively. AZ5104 exhibits a reduced selectivity margin against wild-type EGFR when compared to AZD9291. AZ5104 display minimal off-target activity against other non-HER family kinases, but has the potential to target both HER2 and HER4 kinase activity^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The metabolite, AZ5104 (5 mg/kg/day), is effective in shrinking tumors in both C/L858R and C/L+T mice^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

485.58

C₂₇H₃₁N₇O₂

1421373-98-9

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 28 mg/mL (57.66 mM)

* “≥” means soluble, but saturation unknown.

*

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: ≥ 2.5 mg/mL (5.15 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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: 2.5 mg/mL (5.15 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.15 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.15 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.15 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.

Cells were treated for 2 h with a dose-response of each drug (AZ-5104). Wild-type cells were stimulated for 10 minutes with 25 ng/mL of EGF before lysis. Level of EGFR phosphorylation was quantified in cell extracts using ELISA^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.