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Medicinal-Pharmaceutical Chemistry Commons

Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology

Conference

University of Massachusetts Medical School

Articles 1 - 2 of 2

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang May 2016

Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang

UMass Center for Clinical and Translational Science Research Retreat

Polo-like kinase 1 (PLK1) and BRD4 are two different therapeutic targets in cancer drug discovery. Recently it has been reported that PLK1 inhibitor, BI-2536, is also a potent inhibitor of BRD4. The simultaneous inhibition of PLK1 and BRD4 by a single drug molecule is interesting because this could lead to the development of effective therapeutic strategy for different types of disease conditions in which PLK1 and BRD4 are implicated. Structural activity relationship studies has been carried out on BI-2536 to generate analogs with enhanced dual inhibitory activity against BRD4 and PLK1 as well as to render the molecule selective to ...


Application Of Diarylhydrazones, Schiff-Bases And Their Saturated Derivatives As Multifunctional Inhibitors Of Amyloid Self-Assembly, Christian Schafer, Sanjukta Ghosh, Marianna Torok, Bela Torok May 2014

Application Of Diarylhydrazones, Schiff-Bases And Their Saturated Derivatives As Multifunctional Inhibitors Of Amyloid Self-Assembly, Christian Schafer, Sanjukta Ghosh, Marianna Torok, Bela Torok

UMass Center for Clinical and Translational Science Research Retreat

A new class of multifunctional small molecule inhibitors of amyloid self-assembly is described. Several compounds, based on the diarylhydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and were characterized. The inhibitor candidates were evaluated in multiple assays, including the inhibition of A fibrillogenesis and the disassembly of preformed fibrils. The hydrazone scaffold showed strong activity in inhibiting the amyloid beta self-assembly. The structure-activity relationship revealed that the substituents on the aromatic rings had considerable effect on the overall activity of the compounds. In order to identify possible functional ...