AMG 900 is a potent and highly selectivepan-Aurorakinases inhibitor withIC₅₀of 5 nM, 4 nM and 1 nM forAurora A,BandC, respectively.

AMG 900 inhibits the enzyme activity of all 3 aurora kinase family members with IC₅₀values of 5 nM or less. In HeLa cells, AMG 900 inhibits autophosphorylation of aurora-A and -B in a concentration-dependent manner. Treatment of HCT116 cells with 50 nM of AMG 900 for 48 hours resulted in polyploidy and suppresses the formation of colonies after cell replating. AMG 900 inhibits cell proliferation, with EC₅₀values ranging from 0.7 to 5.3 nM. Importantly, 4 of these AMG 900-sensitive cell lines (HCT-15, MES-SA-Dx5, 769P, and SNU449) are resistant to paclitaxel and other anticancer agents. AMG 900 inhibits p-histone H3 or induced polyploidy across all the cell lines tested irrespective of P-gp or BCRP status with uniform potency (IC₅₀or EC₅₀values ranging from 2 to 3 nM)^[1].

AMG 900 exhibits significant antitumor activity in all 9 xenograft models tested (50%-97% TGI compared with the vehicle-treated control group, P<0.005, P<0.0005). Importantly, AMG 900 is active in the MES-SA-Dx5 (84% TGI, P<0.0001) and NCI-H460-PTX (66% TGI, P<0.0001) xenograft models that are resistant to either Docetaxel or Paclitaxel administered at their respective maximum tolerated doses. AMG 900 inhibits the activity of aurora-B in HCT116 tumors and suppresses the growth of multiple xenografts that represent diverse tumor types^[1]. Treatment with AMG 900 at 15 mg/kg significantly inhibits p-Histone H3 in the G₂M cell population in mouse bone marrow (upper panel) and cytokeratin positive COLO 205 tumor (lower panel) compared with vehicle-treated controls^[2]. AMG 900 exhibits a low-to-moderate clearance and a small volume of distribution. Its terminal elimination half-life ranged from 0.6 to 2.4 h. AMG 900 is well-absorbed in fasted animals with an oral bioavailability of 31% to 107%. Food intake had an effect on rate (rats) or extent (dogs) of AMG 900 oral absorption^[3].

503.58

Solid

C₂₈H₂₁N₇OS

945595-80-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL(99.29 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℃, 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% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 5 mg/mL (9.93 mM); Clear solution

  此方案可获得 ≥ 5 mg/mL (9.93 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-CDin saline)

  Solubility: ≥ 5 mg/mL (9.93 mM); Clear solution

  此方案可获得 ≥ 5 mg/mL (9.93 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 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