BI 2536
BI 2536 is a potent, ATP-competitive, well tolerated and highly specific human polo-like kinase 1 (PLK1) inhibitor with IC value of 0.83 nM, which shows 1000-fold selectivity against other kinases [1].
BI 2536 has been demonstrated to suppress cell growth and colony formation, it has been shown to induce mitotic arrest at G2/M phase and apoptosis in human cervical adenocarcinoma cell line HeLa [2].
BI 2536 has shown to have the effect of inhibiting cell proliferation in more than 20 tumor cell lines with half maximal effective concentration (EC50) values ranging from 2–25 nM. In vivo, multiple studies in xenograft models of human carcinoma have shown the anti-tumor activity of BI 2536 when the drug was intravenously administered 1-2 times every week [1].
References:
[1] Schöffski P. Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
[2] Pezuk JA1, Brassesco MS, Oliveira JC, Morales AG, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG. Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells. Clin Exp Med. 2013 Feb;13(1):75-80.
- 1. Kaisari S, Shomer P, et al. "Role of Polo-like kinase 1 in the regulation of the action of p31(comet) in the disassembly of mitotic checkpoint complexes." Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11725-11730. PMID:31118282
- 2. Chen LL, Wang YB, et al. "Phosphoproteome-based kinase activity profiling reveals the critical role of MAP2K2 and PLK1 in neuronal autophagy." Autophagy. 2017;13(11):1969-1980. PMID:28933595
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 521.67 |
| Cas No. | 755038-02-9 |
| Formula | C28H39N7O3 |
| Synonyms | BI-2536;BI2536 |
| Solubility | insoluble in H2O; ≥13.04 mg/mL in DMSO; ≥92.4 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide |
| SDF | Download SDF |
| Canonical SMILES | CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
HeLa-S3 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 24 hours |
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Applications |
The effect of BI 2536 on the cell-cycle profile of cancer cells grown in vitro was assessed by immunofluorescence microscopy and flow cytometry. BI2536 caused HeLa cells to accumulate with a 4N DNA content, indicative of a cell-cycle block in either G2 phase or mitosis. The mitotic figures observed in BI 2536-treated cultures of HeLa cells displayed abnormal mitotic figures at EC50 values closely matching the induction of a G2/M arrest. |
| Animal experiment: [1] | |
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Animal models |
Immunodeficient nu/nu mice injected with HCT 116 cells |
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Dosage form |
Intravenous injection, 40–50mg/kg, once or twice per week |
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Applications |
The administration of BI 2536 was found to be highly efficacious in diverse xenograft models, such as the HCT 116 colon cancer with complete tumor suppression with the twice per week schedule and a T/C value of 16% with once per week treatment. By using a more rigorous model of larger HCT 116 tumors, in which treatment was delayed until cancer nodules reached a median size of 500 mm3, it was found that five cycles of BI 2536 induced marked tumor regressions, whereas the control mice showed progressive disease. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Steegmaier M, Hoffmann M, Baum A, et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Current Biology, 2007, 17(4): 316-322. | |
| Description | BI2536 is a potent inhibitor of Plk1 with IC50 of 0.83 nM. | |||||
| Targets | Plk1 | |||||
| IC50 | 0.83 nM | |||||
Quality Control & MSDS
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