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Cambridge, MA, United States

Yu T.,2015 Galloping Hill Road | Tagat J.R.,2015 Galloping Hill Road | Kerekes A.D.,2015 Galloping Hill Road | Doll R.J.,2015 Galloping Hill Road | And 24 more authors.
ACS Medicinal Chemistry Letters | Year: 2010

The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B with modest cell potency (IC50 = 250 nM) and low solubility (5 ?M). Lead optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH 1473759), which is a picomolar inhibitor of Aurora kinases (TdF Kd Aur A = 0.02 nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25 nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and target engagement in human tumor xenograft mouse models. © 2010 American Chemical Society.

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