Volasertib (BI 6727) 是一种具有口服活性的、高效的、ATP 竞争性的 Polo 样激酶 1 (PLK1) 抑制剂，IC50为 0.87 nM。Volasertib 抑制 PLK2 和 PLK3，IC50分别为 5 和 56 nM。Volasertib 诱导有丝分裂停滞和细胞凋亡。Volasertib 是一种二氢蝶呤酮衍生物，在多种癌症模型中显示出显着的抗肿瘤活性。
| 生物活性 | Volasertib (BI 6727) is an orally active, highly potent and ATP-competitivePolo-like kinase1 (PLK1)inhibitor with anIC50of 0.87 nM. Volasertib inhibitsPLK2andPLK3withIC50s of 5 and 56 nM, respectively. Volasertib induces mitotic arrest andapoptosis. Volasertib, a dihydropteridinone derivative, shows marked antitumor activity in multiplecancermodels[1][2]. |
| IC50& Target[3] | PLK1 0.87 nM (IC50) | PLK2 5 nM (IC50) | PLK3 56 nM (IC50) |
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体外研究
(In Vitro) | Volasertib (BI 6727; 0.01-10000 nM; 72 hours) has EC50values of 11 to 37 nmol/L in multiple cell lines[1].
Volasertib (10-1000 nM; 24 hours) results accumulation of cells with 4N DNA content, indicative of a cell cycle block in G2-M phase[1].
Volasertib (100 nM; 24-72 hours) induces cell apoptosis at 48 hours[1].
Cell Proliferation Assay[1] | Cell Line: | Multiple cell lines | | Concentration: | 0.01-10000 nM | | Incubation Time: | 72 hours | | Result: | Inhibited proliferation of multiple cell lines derived from various cancer tissues, including carcinomas of the colon (HCT 116, EC50=23 nmol/L) and lung (NCI-H460, EC50=21 nmol/L), melanoma (BRO, EC50=11 nmol/L), and hematopoietic cancers (GRANTA-519, EC50=15 nmol/L; HL-60, EC50=32 nmol/L; THP-1, E50=36 nmol/L and Raji, EC50=37 nmol/L) with EC50values of 11 to 37 nmol/L. |
Apoptosis Analysis[1] | Cell Line: | NCI-H460 cells | | Concentration: | 100 nM | | Incubation Time: | 24, 48, 72 hours | | Result: | G2-M arrest at 24 hours was followed by induction of apoptosis at 48 hours. |
Cell Cycle Analysis[1] | Cell Line: | NCI-H460 cells | | Concentration: | 10, 30, 100, 300, 1000 nM | | Incubation Time: | 24 hours | | Result: | Resulted in accumulation of cells with 4N DNA content, indicative of a cell cycle block in G2-M phase. |
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体内研究
(In Vivo) | Volasertib (BI 6727; A total weekly dose of 50 mg/kg; Oral; once a week, twice a week, or daily; for 40 days) shows comparable efficacy in human colon carcinoma xenograft models[1].
Volasertib (15, 20, or 25 mg/kg/day; i.v.; 2 consecutive days per week; for 40 days) leads to significant tumor growth delay and even tumor regression in human colon carcinoma xenograft models[1].
Volasertib (70 mg/kg given once weekly or 10 mg/kg daily; oral) significantly delays tumor growth in a non-small cell lung carcinoma xenograft model derived from NCI-H460 cells[1].
Volasertib (a single dose of 40 mg/kg; iv) causes a significant (13-fold) increase in mitotic cells in HCT 116 tumor-bearing nude mice[1].
Volasertib has high volume of distribution and a long terminal half-life in mice (Vss=7.6 L/kg, t1/2=46 h) and rats (Vss=22 L/kg, t1/2=54 h)[1].
| Animal Model: | Female BomTac:NMRI-Foxn1numice (Taconic) were grafted s.c. with HCT 116 human colon carcinoma cells (ATCC CCL-247)[1] | | Dosage: | A total weekly dose of 50 mg/kg | | Administration: | Oral; once a week, twice a week, or daily; for 40 days | | Result: | Showed comparable efficacy and were well tolerated. |
| Animal Model: | Female BomTac:NMRI-Foxn1numice and male Wistar rats of the strain Crl:WI[1] | | Dosage: | 35 mg/kg (mice) or 10 mg/kg (rat) (Pharmacokinetic Analysis) | | Administration: | IV 5-minute infusion; a single dose 5-minute infusion | | Result: | Had high volume of distribution and a long terminal half-life in mice (Vss=7.6 L/kg, t1/2=46 h) and rats (Vss=22 L/kg, t1/2=54 h). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(80.80 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.6160 mL | 8.0800 mL | 16.1600 mL | | 5 mM | 0.3232 mL | 1.6160 mL | 3.2320 mL | | 10 mM | 0.1616 mL | 0.8080 mL | 1.6160 mL |
*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 (protect from light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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: ≥ 2.08 mg/mL (3.36 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.36 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.08 mg/mL (3.36 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (3.36 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 20.8 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.36 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.36 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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