Hesperadin
Hersperadin is an ATP-competitive small molecule inhibitor of Aurora B kinase, which is one of the three Aurora family kinases involved in the regulation of cell division, with half maximal inhibitory concentration IC50 of 250 nM, where the sulphonamide group of hersperadin inserts into the ATP-pocket in the catalytic cleft of Aurora B kinase and extends into the adjacent hydrophobic pocket. Hersperadin has been found to prevent the phosphorylation of Aurora B, where the Ser-10 phosphorylation of Aurora B in mitosis serves as a biomarker for mitotic progression, with IC50 of 40 nM leading to inhibition of chromosome alignment and segregation.
References:
[1]Jetton N1, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L. The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol. 2009 Apr;72(2):442-58. doi: 10.1111/j.1365-2958.2009.06657.x. Epub 2009 Mar 6.
[2]Hauf S1, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol. 2003 Apr 28;161(2):281-94. Epub 2003 Apr 21.
- 1. Maik Schuler, Lindsay Tomlinson, et al. "Experiments in the EpiDerm 3D Skin In Vitro Model and Minipigs In Vivo Indicate Comparatively Lower In Vivo Skin Sensitivity of Topically Applied Aneugenic Compounds." Toxicol Sci. 2021 Feb 26;180(1):103-121. PMID:33481035
- 2. 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
- 3. Manuel Saldivia, Srinivasa P.S. Rao, et al. "Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors." bioRxiv. 2019 April 24.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 516.65 |
| Cas No. | 422513-13-1 |
| Formula | C29H32N4O3S |
| Solubility | ≥25.85 mg/mL in DMSO; insoluble in H2O; ≥2.31 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-[(3Z)-2-oxo-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-1H-indol-5-yl]ethanesulfonamide |
| SDF | Download SDF |
| Canonical SMILES | CCS(=O)(=O)NC1=CC2=C(C=C1)NC(=O)C2=C(C3=CC=CC=C3)NC4=CC=C(C=C4)CN5CCCCC5 |
| 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. |
| Vitro experiment [1]: | |
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Kinase experiment |
Hesperadin is an inhibitor that inserts into the ATP-binding pocket of Aurora A and B. It inhibited Aurora B with IC50 of 250 nM, but has IC50 values in the range of 1.2 μM to >10 μM for Cdk1/cyclin B or Cdk2/cyclin E, respectively. At a concentration of 200 nM, Hesperadin lowered the activity of the immunoprecipitated kinase to the background level. |
| Cell experiment [2]: | |
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Cell lines |
HeLa cells |
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Preparation method |
The solubility of this compound in DMSO is >25.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
50 nM; 2 h |
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Applications |
In HeLa cells, Hesperadin stopped cell proliferating but did not stop growing, and over a 6-d period, the cell diameter increased more than sevenfold (from 20 to 150 μm). The cells acquired enlarged lobed nuclei correlated with polyploidization, reaching a 32C DNA content on day 3. Hesperadin caused defects in mitosis and cytokinesis. |
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References: [1]Jetton N1, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L. The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol. 2009 Apr;72(2):442-58. doi: 10.1111/j.1365-2958.2009.06657.x. Epub 2009 Mar 6. [2]Hauf S1, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol. 2003 Apr 28;161(2):281-94. Epub 2003 Apr 21. |
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| Description | Hesperadin is a potent inhibitor of Aurora B with IC50 of 250 nM. | |||||
| Targets | Aurora B (human) | TbAUK1 | ||||
| IC50 | 250 nM | 40 nM | ||||
Quality Control & MSDS
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