title: Identification of a new scaffold for hsp90 C-terminal inhibition.
abstract: Inhibition of Hsp90 C-terminal function is an advantageous therapeutic paradigm for the treatment of cancer. Currently, the majority of Hsp90 C-terminal inhibitors are derived from novobiocin, a natural product traditionally used as an antibiotic. Assisted by molecular docking studies, a scaffold containing a biphenyl moiety in lieu of the coumarin ring system found in novobiocin was identified for development of new Hsp90 C-terminal inhibitors. Initial structure-activity studies led to derivatives that manifest good antiproliferative activity against two breast cancer cell lines through Hsp90 inhibition. This platform serves as a scaffold upon which new Hsp90 C-terminal inhibitors can be readily assembled for further investigation.
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas , Lawrence, Kansas 66045-7563, United States.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR , Via Mario Bianco 9, 20131 Milano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR , Via Mario Bianco 9, 20131 Milano, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas , Lawrence, Kansas 66045-7563, United States.
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
keywords: Heat shock protein 90; Hsp90 C-terminal inhibitors; biphenyl; breast cancer; novobiocin