National Center for
4U93: Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990
Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990
J. Med. Chem. (2014) 57 p.9124-9129
Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.