MLN0905 is a potent PLK1 inhibitor, with an IC₅₀ of 2 nM.

MLN0905 (compound 12c) exhibits potent activities with an EC₅₀ of 33 ± 21 nM for Cdc25C. MLN0905 shows inhibitory effects on HT29, HCT116, H460, and A375 cell lines, with LD₅₀s of 22, 56, 89, and 34 nM^[1]. MLN0905 (125 nM) yields strong mitotic arrest and monopolar spindle formation in HT-29 cells, and these effects are associated with PLK1 inhibition. MLN0905 suppresses lymphoma cell lines with IC₅₀ values ranging from 3 to 24 nM^[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.

MLN0905 (50 mg/kg, p.o.) shows a higher sustained PD response as it impressively generates a robust PD response up to 72 h in nude mice bearing HT29 xenograft tumors. MLN0905 (6.25, 12.5, 25, 50 mg/kg, p.o.) exhibits significant antitumor activities in mice bearing HT29 xenograft tumors^[1]. MLN0905 has marked antitumor effects in a subcutaneous OCI LY-19-Luc lymphoma xenograft model, and the treatment are as follows: 3.12 mg/kg daily, 6.25 mg/kg daily, 10 mg/kg QD×3/wk, and 14.5 mg/kg QD×3/wk. MLN0905 (1.6, 3.12, and 6.25 mg/kg, p.o.) also induces a significant antitumor response in mice bearing disseminated (human) OCI LY-19-Luc lymphoma disease. MLN0905 (6, 8, 10, 12.5, and 14.5 mg/kg, p.o.) causes a significant antitumor response in a primary human lymphoma model (PHTX-22L). Furthermore, MLN0905 synergizes with rituximab in a disseminated OCI LY-19-Luc lymphoma model^[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.

486.56

C₂₄H₂₅F₃N₆S

1228960-69-7

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 : ≥ 30 mg/mL (61.66 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°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: ≥ 2.5 mg/mL (5.14 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.14 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

• 2.

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

  Solubility: ≥ 2.5 mg/mL (5.14 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.14 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 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 (5.14 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.14 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]. Duffey MO, et al. Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). J Med Chem. 2012 Jan 12;55(1):197-208.

  [2]. Shi JQ, et al. MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large B-cell lymphoma. Mol Cancer Ther. 2012 Sep;11(9):2045-53.

The human PLK1 enzymatic reaction totaled 30 μL contains 50 mM Tris-HCl (pH 8.0), 10 mM MgCl₂, 0.02% BSA, 10% glycerol, 1 mM DTT, 100 mM NaCl, 3.3% DMSO, 50 μM ATP, 2 μM peptide substrate (Biotin-AHX-LDETGHLDSSGLQEVHLA-CONH2), and 0.3 nM recombinant human PLK1[2-369]T210D. The enzymatic reaction mixture, with or without PLK inhibitors, is incubated 90 min at room temperature before termination with 50 μL of STOP buffer containing 1% BSA, 0.05% Tween 20, 100 mM EDTA. Then 50 μL of the stopped enzyme reaction mixture is transferred to a Neutravidin-coated 384-well plate and incubated at room temperature for 60 min. The wells are washed with wash buffer (25 mM Tris, 150 mM sodium chloride, and 0.1% Tween 20) and incubated for 1 h with 50 μL of antibody reaction mixture containing 1% BSA, 0.05% Tween 20, antiphospho-cdc25c rabbit monoclonal antibody (325 pM), and europium labeled antirabbit IgG (2 nM). The wells are washed, and then the bound europium is liberated using 50 μL of Enhancement Solution. Quantification of europium is done using a Pherastar^[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.

Eight μL of serially diluted test compounds are added to75 μL of HT29 (2.66×10⁴ cells/well) cells in McCoy’s 5A media supplemented with 10% Fetal Calf Serum in Biocoat Poly-D lysine 384 well Black/Clear plates. Cells are incubated for 72 h at 37°C. Supernatant is aspirated from the wells, leaving 25 μL in each well. ATP-lite 1 step reagent (25 μL) is added to each well, and luminescence for each plate is read on the LeadSeeker. Percent inhibition is calculated using the values from a DMSO control set to 100%^[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.

HT29 cells are obtained from ATCC and are cultured in McCoy’s 5A medium supplemented with 10% FBS. HT29 cells (2×10⁶) are resuspended in Hanks buffer and injected subcutaneously into the flanks of female Nude mice. Mice (10 animals/group) are treated orally with 12c (MLN0905) for 21 days at doses based on tolerability results: QD (6.25 and 12.5 mg/kg), QD×1/week (50 mg/kg), and QD×3/week (25 mg/kg). Tumor growth is monitored using vernier calipers, and the mean tumor volume is calculated using the formula V = W² × L/2. When the mean tumor volume reaches approximately 200 mm³, the animals are randomized into treatment groups (n = 10 animals/group). Tumor growth and body weights are measured twice per week^[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]. Duffey MO, et al. Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). J Med Chem. 2012 Jan 12;55(1):197-208.

  [2]. Shi JQ, et al. MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large B-cell lymphoma. Mol Cancer Ther. 2012 Sep;11(9):2045-53.