GCN2iB is an ATP-competitive inhibitor of a serine/threonine-protein kinase general control nonderepressible 2 (GCN2), with an IC₅₀ of 2.4 nM.

IC50: 2.4 nM (GCN2)^[1].

GCN2iB shows an IC₅₀ value of 2.4 nM for GCN2 and potent cellular activity. In a panel of 468 kinases, only GCN2 shows >99.5% inhibition, and three kinases (MAP2K5, STK10, and ZAK) show >95%inhibition at 1 μM GCN2iB, demonstrating high kinase selectivity^[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.

In the antitumor activity study of the CCRF-CEM xenografts, ASNase or GCN2iB alone does not significantly affect tumor growth. Notably, a combination of ASNase and GCN2iB elicit potent antitumor activity (P=0.0002) with synergistic effects. In MV-4-11 and SU.86.86 xenografts, robust antitumor activity of the combination of GCN2iB and ASNase is observed with synergistic effect, respectively. ASNase/GCN2iB-treated tumors do not show significant growth even after drug cessation. The combination of ASNase and GCN2iB yield survival advantage compared with the vehicle treated control with synergistic effect^[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.

451.83

C₁₈H₁₂ClF₂N₅O₃S

2183470-12-2

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 : 16.67 mg/mL (36.89 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°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: ≥ 1.67 mg/mL (3.70 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.70 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 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% corn oil

  Solubility: ≥ 1.67 mg/mL (3.70 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.70 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 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Nakamura A, et al. Inhibition of GCN2 sensitizes ASNS-low cancer cells by disrupting the amino acid response. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7776-E7785.

Mice^[1]
A suspension of CCRF-CEM, HPB-ALL, MV-4-11, or SU.86.86 cells (1×10⁷ cells/site) is subcutaneously injected into the right flanks of 6-week-old female SCID mice. Tumor volume is calculated as volume =L×l²×1/2, where L represents the longest diameter across the tumor and l represents the corresponding perpendicular distance. Body weight is also measured. To assess the anti-tumor activity, mice with tumor mass ~200 mm³ are sorted into treatment groups (N=5/group). The tumors are monitored and mice are euthanized when an endpoint is reached, or at the end of the study, whichever comes first. From the next day of randomization, GCN2 inhibitors (e.g., GCN2iB, 10 mpk, twice a day) or ASNase is orally or intraperitoneally administered to mice bearing the xenografts for 7 to 10 days, respectively. T/C (%), an index of anti-tumor activity, is calculated by comparing the mean change in tumor volume during the treatment period in the control and treated groups^[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]. Nakamura A, et al. Inhibition of GCN2 sensitizes ASNS-low cancer cells by disrupting the amino acid response. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7776-E7785.