Antibodies
BI 2536
- 貨號 Cat. No.
- S1109
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
BI 2536
BI2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM. It shows 4- and 11-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 | BI2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM. It shows 4- and 11-fold greater selectivity against Plk2 and Plk3. Phase 2. | |||||
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| Targets | Plk1 | |||||
| IC50 | 0.83 nM [1] | |||||
| In vitro | BI 2536 blocks the activities of Plk2 and Plk3 to a slightly lesser extent with IC50 of 3.5 nM and 9.0 nM, respectively. In HeLa cells, BI 2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes that are known to depend on Plk1. BI 2536 treatment leads to the HeLa cells arrested in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50 of 12-31 nM. [1] Plk1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. [2] | |||||
| In vivo | BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. [1] | |||||
| Features | The first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Plk1 in vitro kinase assay | Recombinant human Plk1 (residues 1-603) is expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1 are performed in the presence of serially diluted BI 2536 with 20 ng of recombinant kinase and 10 μg casein from bovine milk as the substrate. Kinase reactions are performed 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 mM ATP, 0.3 μCi γ-33P-ATP). Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curve is used for calculating IC50 value. |
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Cell Assay: [1]
| Cell lines | HeLa, A43, SKOV-3, HT-29, K562, A549, Saos-2, MCF7, HCT116, COLO 205, Hep G2, Raji and PC-3 cells, etc. |
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| Concentrations | Dissolved in DMSO, final concentrations ~1 μM |
| Incubation Time | 24 and 72 hours |
| Method | Cells are exposed to various concentrations of BI 2536 for 24, and 72 hours. Cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. For determining the DNA content of the cultures, 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 (PI) in PBS for 20 minutes at RT. Cell-cycle profiles are determined by flow cytometric analysis. |
Animal Study: [1]
| Animal Models | Female BomTac:NMRI-Foxn1nu mice injected subcutaneously with HCT 116, NCI-H460, or A549 cells |
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| Dosages | ~50 mg/kg |
| Administration | Injection i.v. once or twice per week |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 15 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00243087 | Completed | Lymphoma | Boehringer Ingelheim Pharmaceuticals | 2005-07 | Phase 1 |
| NCT00376623 | Completed | Carcinoma, Non-Small-Cell Lung | Boehringer Ingelheim Pharmaceuticals | 2006-04 | Phase 2 |
| NCT00710710 | Completed | Pancreatic Neoplasms | Boehringer Ingelheim Pharmaceuticals | 2006-08 | Phase 2 |
| NCT00701766 | Completed | Leukemia, Myeloid, Acute | Boehringer Ingelheim Pharmaceuticals | 2006-10 | Phase 2 |
| NCT00526149 | Active, not recruiting | Breast Cancer|Endometrial Cancer|Head and Neck Cancer|Melanoma (Skin)|Ovarian Cancer|Sarcoma | National Cancer Institute (NCI)|European Organisation for Research and Treatment of Cancer - EORTC | 2007-07 | Phase 2 |
Chemical Information
| Molecular Weight (MW) | 521.66 |
|---|---|
| Formula | C28H39N7O3 |
| CAS No. | 755038-02-9 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 21 mg/mL (40 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 100 mg/mL (191 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 15 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 | (R)-4-(8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.52166 | 5.2166 | 10.4332 | 15.6498 |
Customer Reviews (10)
 Click to enlarge | Rating | |
| Source | Cancer Res 2011 71, 1385-1395. BI 2536 purchased from Selleck | |
| Method | Tumor growth assay | |
| Cell Lines | NOD/SCID mice | |
| Concentrations | 12.5-25 mg/kg | |
| Incubation Time | 0-24 d | |
| Results | As shown in Figure A,tumor growth was significantly inhibited following administration of the third cycle of BI 2536 therapy. When mice were administered 25 mg/ kg weekly on 2 consecutive days for a total of only 2 cycles, tumor growth was inhibited after the second cycle ( Fig. B) |
Product Citations (22)
Systematic discovery of TLR signaling components delineates viral-sensing circuits. [Chevrier N, et al. Cell 2011;4(10):1087-96]
Targeting mitotic exit leads to tumor regression in vivo: modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase. [Manchado E, et al. Cancer Cell 2010;18(6):641-54]
Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. [Foley EA, et al. Nat Cell Biol 2011;13(10):1265-71]
