422513-13-1

Hesperadin is a multi-kinase inhibitor. It inhibits human Aurora kinase B (IC₅₀ = 250 nM) and its T. brucei homolog Aurora kinase-1 (IC₅₀ = 40 nM) in in vitro kinase assays. Hesperadin (1 μM) inhibits AMPK, LCK, MKK1, MAPKAP-K1, CHK1, and PHK in a panel of 25 kinases. It also inhibits MEKK2 in ATPase and transphosphorylation assays with IC₅₀s of 60 and 34 nM, respectively. Hesperadin (50-100 nM) induces polyploidy and defects in cytokinesis and spindle assembly as well as inhibits proliferation of HeLa cells and overrides mitotic arrest induced by paclitaxel or monastrol . Hesperadin also induces toxicity in HepG2 cells with a toxic concentration (TC₅₀) value of less than 0.2 μM. It inhibits replication of clinical isolates of influenza A and B viruses with EC₅₀s ranging from 0.22 to 2.21 μM in a plaque formation assay. Hesperadin inhibits the growth of T. brucei, L. major promastigotes and amastigotes, and P. falciparum with EC₅₀ values ranging from 0.01 to 2.37 μM, but has less activity against T. cruzi (EC₅₀ = 39 μM).

Hesperadin phosphorylates human mitotic protein complexes that control physiological changes within the cell to allow for proper and successful chromosome segregation. It also targets aurora kinases i n cancer treatment, affecting the chromosomes’regulation during mitosis.

ChEBI: An oxindole that is indolin-2-one which is substituted at position 5 by an (ethylsulfonyl)nitrilo group and at position 2 by a methylidene group, which is itself substituted by a phenyl group and a [4-(piperidin-1-ylmethyl)phenyl]amino group. An Aurora B k nase inhibitor, it is used to inhibit chromosome alignment and segregation.

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[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.