HesperadinAurora B kinase inhibitor CAS# 422513-13-1 |
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Quality Control & MSDS
3D structure
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| Cas No. | 422513-13-1 | SDF | Download SDF |
| PubChem ID | 10142586 | Appearance | Powder |
| Formula | C29H32N4O3S | M.Wt | 516.65 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (193.55 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-[(3Z)-2-oxo-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-1H-indol-5-yl]ethanesulfonamide | ||
| SMILES | CCS(=O)(=O)NC1=CC2=C(C=C1)NC(=O)C2=C(C3=CC=CC=C3)NC4=CC=C(C=C4)CN5CCCCC5 | ||
| Standard InChIKey | GLDSKRNGVVYJAB-DQSJHHFOSA-N | ||
| Standard InChI | InChI=1S/C29H32N4O3S/c1-2-37(35,36)32-24-15-16-26-25(19-24)27(29(34)31-26)28(22-9-5-3-6-10-22)30-23-13-11-21(12-14-23)20-33-17-7-4-8-18-33/h3,5-6,9-16,19,30,32H,2,4,7-8,17-18,20H2,1H3,(H,31,34)/b28-27- | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | ATP-competitive inhibitor of Aurora B kinase (IC50 = 250 nM). Prevents chromosome alignment and segregation; also induces polyploidy and prevents histone H3-Ser10 phosphorylation. Overrides the spindle assembly checkpoint and induces mitotic exit in monastrol- and taxol -treated HeLa cells. |
Hesperadin Dilution Calculator
Hesperadin Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9355 mL | 9.6777 mL | 19.3555 mL | 38.7109 mL | 48.3887 mL |
| 5 mM | 0.3871 mL | 1.9355 mL | 3.8711 mL | 7.7422 mL | 9.6777 mL |
| 10 mM | 0.1936 mL | 0.9678 mL | 1.9355 mL | 3.8711 mL | 4.8389 mL |
| 50 mM | 0.0387 mL | 0.1936 mL | 0.3871 mL | 0.7742 mL | 0.9678 mL |
| 100 mM | 0.0194 mL | 0.0968 mL | 0.1936 mL | 0.3871 mL | 0.4839 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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.
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[Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells].[Pubmed:15945350]
Biomed Khim. 2005 Mar-Apr;51(2):170-6.
Aurora B, which is important for cell division control, is highly expressed in large number of cancer cell lines. Hesperadin, a prototype of a pharmacological agent, is a small molecule inhibitor of catalytic activity of Aurora B. In present work we investigate effect of Hesperadin on breast--MCF7 and prostate adenocarcinoma--PC3, cancer cell lines. After Hesperadin treatment we observe stop of cell proliferation due to appearance of multiple mitotic defects caused by Aurora B activity reduction and elimination of checkpoint proteins--such as hBUBR1 and CENP-E--from kinetochores of mitotic chromosomes.
Mechanism of Aurora B activation by INCENP and inhibition by hesperadin.[Pubmed:15866179]
Mol Cell. 2005 Apr 29;18(3):379-91.
Aurora family serine/threonine kinases control mitotic progression, and their deregulation is implicated in tumorigenesis. Aurora A and Aurora B, the best-characterized members of mammalian Aurora kinases, are approximately 60% identical but bind to unrelated activating subunits. The structure of the complex of Aurora A with the TPX2 activator has been reported previously. Here, we report the crystal structure of Aurora B in complex with the IN-box segment of the inner centromere protein (INCENP) activator and with the small molecule inhibitor Hesperadin. The Aurora B:INCENP complex is remarkably different from the Aurora A:TPX2 complex. INCENP forms a crown around the small lobe of Aurora B and induces the active conformation of the T loop allosterically. The structure represents an intermediate state of activation of Aurora B in which the Aurora B C-terminal segment stabilizes an open conformation of the catalytic cleft, and a critical ion pair in the kinase active site is impaired. Phosphorylation of two serines in the carboxyl terminus of INCENP generates the fully active kinase.
Synthesis and investigation of new Hesperadin analogues antitumor effects on HeLa cells.[Pubmed:25077005]
J Chem Biol. 2014 May 18;7(3):85-91.
Hesperadin is one of the indolinones that was designed against the ATP-binding site of Aurora kinase. This molecule inhibits Aurora B kinase by phosphorylation of histone H3. In this study, new derivatives of Hesperadin containing an amide group in their structures were synthesized through sequential Ugi/palladium-catalyzed approach and in vitro antitumor activity of new compounds were evaluated by cell proliferation assay. The results show that compounds 6f, 6i, 6l, and 6o were dose-dependently inhibited in different concentrations, and IC50 values were between 35 and 43 nM. It seems that lipophilic substitution on the indolinone core with the ability to form additional hydrogen bond might lead to increased stability of structure and activity of new Hesperadin analogues.
The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms.[Pubmed:19320832]
Mol Microbiol. 2009 Apr;72(2):442-58.
Aurora kinase family members co-ordinate a range of events associated with mitosis and cytokinesis. Anti-cancer therapies are currently being developed against them. Here, we evaluate whether Aurora kinase-1 (TbAUK1) from pathogenic Trypanosoma brucei might be targeted in anti-parasitic therapies as well. Conditional knockdown of TbAUK1 within infected mice demonstrated its essential contribution to infection. An in vitro kinase assay was developed which used recombinant trypanosome histone H3 as a substrate. Tandem mass spectroscopy identified a novel phosphorylation site in the carboxyl-tail of recombinant trypanosome histone H3. Hesperadin, an inhibitor of human Aurora B, prevented the phosphorylation of substrate with IC(50) of 40 nM. Growth of cultured bloodstream forms was also sensitive to Hesperadin (IC(50) of 50 nM). Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Consequently, growth arrested cells accumulated multiple kinetoplasts, flagella and nucleoli, similar to the effects of RNAi-dependent knockdown of TbAUK1 in cultured bloodstream forms cells. Molecular models predicted high-affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Collectively, these data demonstrate that cell cycle progression is essential for infections with T. brucei and that parasite Aurora kinases can be targeted with small-molecule inhibitors.
The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.[Pubmed:12707311]
J Cell Biol. 2003 Apr 28;161(2):281-94.
The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3-5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.
