AZD-7762 is a potent ATP-competitivecheckpoint kinase(Chk) inhibitor in with anIC₅₀of 5 nM forChk1.

AZD-7762 (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G₂checkpoints, enhances the efficacy of NSC 613327 and SKF 104864A, and modulates downstream checkpoint pathway proteins. AZD-7762 potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC₅₀of 5 nM as measured by a scintillation proximity assay. The K_ifor AZD-7762 is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 is shown to abrogate the G₂arrest induced by Camptothecin with an average EC₅₀of 10 nM (n=12) and maximal abrogation in the range of 100 nM^[1].

In the rat H460-DNp53 xenograft study, AZD-7762 (AZD7762) potentiates the antitumor activity of NSC 613327 in a dose-dependent manner by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD-7762, respectively). In the mouse xenograft study in combination with CPT-11, SW620 established tumors are treated with vehicle, CPT-11 alone, AZD-7762 alone, or AZD-7762 in combination with CPT-11. AZD-7762 dosed alone shows insignificant antitumor activity, whereas CPT-11 alone displays striking and significant activity (%T/C with increasing dose is 9 and 1, respectively ). In combination with AZD-7762, %T/C increases significantly to -66% and -67%, respectively^[1]. AZD7762 combination with CX-5461 induces cancer cell death ofTp53-null (Tp53^-/-) Eμ-Myclymphoma cells in vitro and in vivo^[2].

362.42

Solid

C₁₇H₁₉FN₄O₂S

860352-01-8

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL(275.92 mM;Need ultrasonic)

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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

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%HP-β-CD

  Solubility: 10 mg/mL (27.59 mM); Clear solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (6.90 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.90 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (6.90 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.90 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 900 μL20% 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (6.90 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.90 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。