AZD1208 is an orally bioavailable, highly selective PIM kinases inhibitor^[1].

AZD1208 shows good antiproliferative activity in a megakaryoblastic leukemia cell line, MOLM-16, with GI₅₀ values less than 100 nM^[1]. AZD1208 (10 μM) inhibits the growth of Ramos cells, and at 1 μM, strongly inhibits PIM kinases in all cell at 1 μM. AZD1208 induces apoptosis, and PIM2 knockdown is mainly associated with an alteration of the cell cycle^[2]. The combination of AZD1208 and AZD2014 rapidly activates AMPKα, a negative regulator of translation machinery through mTORC1/2 signaling in AML cells; profoundly inhibits AKT and 4EBP1 activation; and suppresses polysome formation^[3].

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.

379.48

C₂₁H₂₁N₃O₂S

1204144-28-4

Room temperature in continental US; may vary elsewhere.

DMSO : 66.67 mg/mL (175.69 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。

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: ≥ 5 mg/mL (13.18 mM); Clear solution

  此方案可获得 ≥ 5 mg/mL (13.18 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 50.0 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: 5 mg/mL (13.18 mM); Suspended solution; Need ultrasonic

  此方案可获得 5 mg/mL (13.18 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 50.0 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 (6.59 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.59 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Dakin LA, et al. Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604.

  [2]. Kreuz S, et al. Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas. Mol Cancer. 2015 Dec 8;14:205.

  [3]. Harada M, et al. The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression. Oncotarget. 2015 Nov 10;6(35):37930-47.

MOLM-16 cells, purchased from DSMZ and cultured in RPMI containing 10% fetal bovine serum (FBS) and 1% L-glutamine, are plated at 20,000 cells per well in 96 well plates overnight. Cells are treated for 72 hours with compound or control vehicle (dimethyl sulfoxide) and cell viability is measured after the addition of Cell Titer-Blue for 4 hours at 37°C and reading of fluorescence on a Tecan Infinite^® 200. The GI₅₀ is determined by calculating growth at each dose relative to vehicle treated cells and cell viability at the time of treatment.

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]. Dakin LA, et al. Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604.

  [2]. Kreuz S, et al. Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas. Mol Cancer. 2015 Dec 8;14:205.

  [3]. Harada M, et al. The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression. Oncotarget. 2015 Nov 10;6(35):37930-47.