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Hesperadin

Names

[ CAS No. ]:
422513-13-1

[ Name ]:
Hesperadin

[Synonym ]:
N-[(3Z)-2-Oxo-3-(phenyl{[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)-2,3-dihydro-1H-indol-5-yl]ethanesulfonamide
N-[(3Z)-2-oxo-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-1H-indol-5-yl]ethanesulfonamide
S1529_Selleck
UNII-PTR491OS14
Ethanesulfonamide, N-[(3Z)-2,3-dihydro-2-oxo-3-[phenyl[[4-(1-piperidinylmethyl)phenyl]amino]methylene]-1H-indol-5-yl]-
Hesperadin
TCMDC-135395
cc-473
N-[(3Z)-2-Oxo-3-(phenyl{[4-(1-piperidinylmethyl)phenyl]amino}methylene)-2,3-dihydro-1H-indol-5-yl]ethanesulfonamide

Biological Activity

[Description]:

Hesperadin is an ATP-competitive inhibitor of aurora B kinase with an IC50 of 250 nM.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Aurora Kinase
Signaling Pathways >> Epigenetics >> Aurora Kinase
Signaling Pathways >> Autophagy >> Autophagy
Research Areas >> Cancer

[Target]

Aurora B:250 nM (IC50)


[In Vitro]

Hesperadin also inhibits other kinases such as AMPK, Lck, MKK1, MAPKAP-K1, CHK1, and PHK at 1 µM drug concentration. Hesperadin causes polyploidy in HeLa cells. Hesperadin-treated HeLa cells show alignment and segregation defects, but sister chromatid separation is intact. Hesperadin causes defects in mitosis and cytokinesis. Hesperadin inhibits Aurora B. Immunofluorescence microscopy reveals that Hesperadin-treated cells in which chromosomes are stretched toward opposite poles, i.e., which have entered anaphase, fail to assemble a central spindle and to properly localize the human centralspindlin subunits CYK-4 and MKLP1[1]. Hesperadin inhibits multiple human clinical isolates of influenza A and B viruses with single to submicromolar efficacy, including oseltamivir-resistant strains. Mechanistic studies reveal that hesperadin inhibits the early stage of viral replication by delaying the nuclear entry of viral ribonucleoprotein complex, thereby inhibiting viral RNA transcription and translation as well as viral protein synthesis[2]. Hesperadin inhibits cell 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[3].

[Kinase Assay]

The kinase assay is performed with 10 μL beads in 20 μL kinase buffer containing 5 g histone H1, 1 μM ATP, 1 μCi [32P]ATP, and the appropriate concentration of Hesperadin or DMSO for 30 min at 37C. SDS sample buffer is added, and samples are boiled and resolved by SDS-PAGE. The gel is dried, and the radioactive signal is detected by PhosphorImager analysis[1].

[Cell Assay]

To determine cellular cytotoxicity of Hesperadin, 200 µL fresh DMEM (without FBS) medium containing serial half-log diluted Hesperadin is added to each well. After incubating for 48 h with 5% CO2 in the cell culture incubator at 37 °C, the medium is removed and 100 µL DMEM medium containing 40 µg/mL neutral red is added. The solution is incubated for another 4 h at 37 °C in the cell culture incubator. The medium is removed and the amount of neutral red that is taken by the viable cells is dissolved by adding 100 µL of destaining solution (50% ethanol, 49% H2O, and 1% acetic acid). The absorbance of the solution at 540 nm is determined[2].

[References]

[1]. Hauf S, et al. 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.

[2]. Hu Y, et al. Chemical Genomics Approach Leads to the Identification of Hesperadin, an Aurora B Kinase Inhibitor, as a Broad-Spectrum Influenza Antiviral. Int J Mol Sci. 2017 Sep 8;18(9).

[3]. Ladygina NG, et al. Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells. Biomed Khim. 2005 Mar-Apr;51(2):170-6.


[Related Small Molecules]

Alisertib (MLN8237) | Tozasertib | AT9283 | Barasertib (AZD1152-HQPA) | danusertib | Reversine | MLN8054 | GSK1070916 | AMG-900 | KW-2449 | TAK-632 | TAK-901 | MK-5108(VX-689) | pf-03814735 | ENMD-2076

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Molecular Formula ]:
C29H32N4O3S

[ Molecular Weight ]:
516.654

[ Exact Mass ]:
516.219482

[ PSA ]:
102.41000

[ LogP ]:
3.13

[ Index of Refraction ]:
1.675

[ Storage condition ]:
-20°C

Related Compounds