Hesperadin is an inhibitor of human Aurora B, which can prevent 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. (See: Mol Microbiol. 2009 Apr;72(2):442-58. or http://www.ncbi.nlm.nih.gov/pubmed/19320832).

MedKoo Cat#: 201466 Name: Hesperadin CAS#: 422513-13-1 Chemical Formula: C29H32N4O3S Exact Mass: 516.21951 Molecular Weight: 516.65 Elemental Analysis: C, 67.42; H, 6.24; N, 10.84; O, 9.29; S, 6.21

Synonym: Hesperadin

IUPAC/Chemical Name: (Z)-N-(2-oxo-3-(phenyl((4-(piperidin-1-ylmethyl)phenyl)amino)methylene)indolin-5-yl)ethanesulfonamide

InChi Key: GLDSKRNGVVYJAB-DQSJHHFOSA-N

InChi Code: 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/h4,5-6,9-16,19,30,32H,2,4,7-8,17-18,20H2,1H3,(H,31,34)/b28-27-

SMILES Code: CCS(=O)(NC1=CC2=C(NC(/C2=C(C3=CC=CC=C3)NC4=CC=C(CN5CCCCC5)C=C4)=O)C=C1)=O

Technical Data

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Certificate of Analysis: View current batch of CoA

QC Data: View NMR, View HPLC, View MS

Safety Data Sheet (MSDS): View Material Safety Data Sheet (MSDS)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

     

References

1: Jetton N, 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. PubMed PMID: 19320832; PubMed Central PMCID: PMC2697958.

2: Ladygina NG, Latsis RV, Yen T. [Effect of the pharmacological agent hesperadin on breast and prostate tumor cultured cells]. Biomed Khim. 2005 Mar-Apr;51(2):170-6. Russian. PubMed PMID: 15945350.

3: Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell. 2005 Apr 29;18(3):379-91. PubMed PMID: 15866179.

4: Hauf S, 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. PubMed PMID: 12707311; PubMed Central PMCID: PMC2172906.