CCT 137690 is a potent and orally available aurora kinase inhibitor with IC₅₀s of 15, 25, and 19 nM for aurora A, B and C, respectively.

CCT 137690 displays antiproliferative activity in a range of human tumor cell lines, including SW620 colon carcinoma (GI₅₀=0.30 μM) and A2780 ovarian cancer cell line (GI₅₀=0.14 μM). CCT 137690 inhibits in vitro phosphorylation of histone H3. CCT 137690 is a moderate inhibitor of the hERG ion-channel (IC₅₀=3.0 μM)^[1]. CCT137690 efficiently inhibits histone H3 and TACC3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumour cells to the inhibitor causes multipolar spindle formation, chromosome misalignment, polyploidy and apoptosis^[2].

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.

CCT 137690 slows the growth of the SW620 xenografts with no observed toxicity^[1]. CCT 137690 significantly inhibits tumour growth in a transgenic mouse model of neuroblastoma (TH-MYCN) that overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma formation^[2].

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.

551.48

C₂₆H₃₁BrN₈O

1095382-05-0

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 (30.23 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 (3.03 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.03 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 1.67 mg/mL (3.03 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.03 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 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: ≥ 1.67 mg/mL (3.03 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (3.03 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]. Bavetsias V, et al. Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28.

  [2]. Faisal A, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115-23.

Cells are plated in 96-well plates at 3,000 cells per well and are treated with a range of 0 to 25 mol/L of CCT137690 for 72 h. Cell proliferation assays are performed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)^[2].

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.

Mice: Animals are randomized into two groups, group 1: treatment with 100 mg/kg CCT137690 n=4 or group 2: vehicle control n=4. Treatment is administered via oral gavage twice daily. Tumour volumes are measured at day 0, 3 (48 hours after treatment started), 7 and 10 using ¹H MRI^[2].

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]. Bavetsias V, et al. Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28.

  [2]. Faisal A, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115-23.