6533b82ffe1ef96bd1295c5d

RESEARCH PRODUCT

Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

Ronald M. ParanalMariangela LibrizziPeter CoxheadJohn SpencerJohn SpencerHiren PatelIrina ChuckowreeIrina ChuckowreeJames E. BradnerMatthew GuilleMinghua WangAlexandra M. E. ZuckermannRobin S.b. Williams

subject

PharmacologyHistone deacetylase 5medicine.drug_classKinaseHistone deacetylase 2Organic ChemistryHistone deacetylase inhibitorQPharmaceutical ScienceBiologyBiochemistryHDACiVEGFRiHybrids.BiochemistryDocking (molecular)In vivoDrug DiscoverymedicineMolecular MedicineHistone deacetylaseSettore BIO/06 - Anatomia Comparata E CitologiaSemaxanibmedicine.drug

description

Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2\ud inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been\ud merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is\ud provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well\ud as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-\ud N8-hydroxyoctanediamide 6.

yearjournalcountryeditionlanguage
2014-06-18
10.1039/c4md00211chttp://sro.sussex.ac.uk/id/eprint/50416/1/c4md00211c.pdf