Antibodies
Volasertib (BI 6727)
- 貨號 Cat. No.
- S2235
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Volasertib (BI 6727)
BI6727 (Volasertib) is a highly potent Plk1 inhibitor with IC50 of 0.87 nM. It shows 6- and 65-fold greater selectivity against Plk2 and Plk3. Phase 2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | BI6727 (Volasertib) is a highly potent Plk1 inhibitor with IC50 of 0.87 nM. It shows 6- and 65-fold greater selectivity against Plk2 and Plk3. Phase 2. | |||||
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| Targets | Plk1 | |||||
| IC50 | 0.87 nM [1] | |||||
| In vitro | Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, BI6727 also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. BI6727 at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. BI6727 inhibits the proliferation of multiple cell lines derived from various cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells with EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively. BI6727 treatment (100 nM) in NCI-H460 cells induces an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, confirming that cells are arrested early in the M phase, followed by induction of apoptosis. [1] Low nanomolar concentrations of BI6727 display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of BI6727 are cytotoxic for normal pediatric neural stem cells. [2] BI6727 induces growth arrest of Daoy and ONS-76 medulloblastoma cells similar to BI 2536. [3] | |||||
| In vivo | Administration of BI6727 significantly inhibits the growth of multiple human carcinoma xenografts including HCT116, NCI-H460, and taxane-resistant CXB1 colon carcinoma, accompanied by an increase in the mitotic index as well as an increase in apoptosis. [1] In in vivo studies, BI6727 shows better toxicity and pharmacokinetic profile compared to BI2536. [3] | |||||
| Features | A high volume of distribution, indicating good tissue penetration, and a long terminal half-life. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| In vitro kinase assays | Recombinant human Plk1 (residues 1-603) is expressed as NH2-terminal, GST-tagged fusion protein using a baculoviral expression system and purified by affinity chromatography using glutathione-agarose. Enzyme activity assays for Plk1 are done in the presence of serially diluted BI6727 using 20 ng of recombinant kinase and 10 μg casein from bovine milk as substrate. Kinase reactions are done in a final volume of 60 μL for 45 minutes at 30 °C [15 mM MgCl2, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi γ-32P-ATP]. Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transferring the precipitates to MultiScreen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curves are used for calculating IC50 value. |
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Cell Assay: [1]
| Cell lines | HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji |
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| Concentrations | Dissolved in DMSO, final concentrations ~1 μM |
| Incubation Time | 24, 48, and 72 hours |
| Method | Cell proliferation assays are done by incubating cells in the presence of various concentrations of BI6727 for 24, 48, and 72 hours and cell growth is assessed by measuring Alamar blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth is inhibited by 50% (EC50) are extrapolated from the dose-response curve fit. To determine the DNA content, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide in PBS for 20 minutes at room temperature. Cell cycle profiles are determined by flow cytometric analysis. |
Animal Study: [1]
| Animal Models | Female BomTac:NMRI-Foxn1nu mice grafted s.c. with HCT116, NCI-H460, or CXB1 cells |
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| Dosages | ~25 mg/kg/day |
| Administration | Injected i.v., or given intragastrally via gavage needle |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01022853 | Completed | Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2009-12 | Phase 1 |
| NCT01121406 | Active, not recruiting | Ovarian Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2010-04 | Phase 2 |
| NCT01145885 | Completed | Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2010-06 | Phase 1 |
| NCT01206816 | Completed | Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2010-10 | Phase 1 |
| NCT01348347 | Active, not recruiting | Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2011-04 | Phase 1 |
Chemical Information
Download Volasertib (BI 6727) SDF
| Molecular Weight (MW) | 618.81 |
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| Formula | C34H50N8O3 |
| CAS No. | 755038-65-4 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 50 mg/mL (80 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 124 mg/mL (200 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | N-((1r,4r)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-4-((R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-ylamino)-3-methoxybenzamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.61881 | 6.1881 | 12.3762 | 18.5643 |
Customer Reviews (2)
 Click to enlarge | Rating | |
| Source | Dr. Xiangbing Meng from University of Iowa. Volasertib (BI 6727) purchased from Selleck | |
| Method | Western blot, MTT assays | |
| Cell Lines | Hec50 cells | |
| Concentrations | 0-50 nM | |
| Incubation Time | 3 d | |
| Results | Reduction of Cdc2 Tyr15 phosphorylation and increase Histone H3 Ser10 phosphorylation in cells treated with BI 6727 was observed. |
Product Citations (3)
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res 2013;73(20):6310-22]
p21Waf1/Cip1 deficiency causes multiple mitotic defects in tumor cells. [Kreis NN, et al. Oncogene 2013;10.1038/onc.2013.518]
A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. [Danovi D, et al. PLoS One 2013;8(10):e77053]
