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BI 2536Plk1 inhibitor,potent and ATP-competitive

BI 2536

Catalog No. A3965
Size Price Stock Qty
10mM (in 1mL DMSO) $125.00 In stock
Evaluation Sample $28.00 In stock
5mg $85.00 In stock
10mg $150.00 In stock
50mg $470.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

BI 2536

Related Biological Data

BI 2536

Biological Activity

Description BI2536 is a potent inhibitor of Plk1 with IC50 of 0.83 nM.
Targets Plk1          
IC50 0.83 nM          

Protocol

Cell experiment: [1]

Cell lines

HeLa-S3 cells

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.

Reaction Conditions

1 μM, 24 hours

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]

Animal models

Immunodeficient nu/nu mice injected with HCT 116 cells

Dosage form

Intravenous injection, 40–50mg/kg, once or twice per week

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.

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.

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.

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Chemical Properties

Cas No. 755038-02-9 SDF Download SDF
Synonyms BI-2536;BI2536
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
Canonical SMILES CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C
Formula C28H39N7O3 M.Wt 521.67
Solubility >13mg/mL in DMSO Storage Store at -20°C
General tips No
Shipping Condition No

Research Update

1. Human ABCB1 (P-glycoprotein) and ABCG2 mediate resistance to BI 2536, a potent and selective inhibitor of Polo-like kinase 1. Biochem Pharmacol. 2013 Oct 1;86(7):904-13. doi: 10.1016/j.bcp.2013.08.004. Epub 2013 Aug 17.
Abstract
BI 2536, a Plk1 inhibitor, exhibits antiproliferative activity against cancer cells through promoting G2/M cell cycle arrest. Acquired BI 2536 resistance in ABCB1 or ABCB2 overexpressing human cancer cells is caused by BI 2536 induced inhibition of drug substrate transport mediated by ABC transporters and can be diminished by addition of inhibitors of ABC transporters.
2. A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer. Clin Lung Cancer. 2013 Jan;14(1):19-27. doi: 10.1016/j.cllc.2012.04.003. Epub 2012 Jun 1.
Abstract
The combination of BI 2536, a PlK1 inhibitor, and pemetrexed was evaluated for MTD, safety, efficacy and PK in previously treated advanced or metastatic non-small-cell lung cancer.
3. A randomized, open-label, phase I/II trial to investigate the maximum tolerated dose of the Polo-like kinase inhibitor BI 2536 in elderly patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2013 Oct;163(2):214-22. doi: 10.1111/bjh.12518. Epub 2013 Aug 16.
Abstract
BI 2536, a Plk inhibitor capable of inducing mitotic arrest and apoptosis, showed modest clinical activity (9% response rate) in elderly patients with relapsed/refractory AML, which increased bone marrow cells in G2/M with a characteristic pattern of mitotic catastrophe and caused haematological side effects.
4. PLK1 expression and BI 2536 effects in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014 Feb 12. doi: 10.1002/pbc.24978. [Epub ahead of print]
Abstract
PLK1, a mitotic events mediating kinase, is associated with poorly prognosed neoplasia and has not been assessed for its role in childhood ALL.
5. Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels. Neoplasia. 2012 May;14(5):410-9.
Abstract
BI 2536, a Plk1 inhibitor, reduced HCC cell viability, inhibited HCC xenograft progression in nude mice and diminished hepatocarcinogenesis in TGF α/c-myc bitransgenic mice. However, BI 2536 hardly affect HCC progression in the transgenic mouse HCC model due to resistance caused by low intratumoral levels of BI 2536.

Background

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.