Poster Session

Start Date

20-5-2016 12:30 PM

Document Type

Poster Abstract

Description

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 one target over the other. UMB101 and 160 have been found to exhibit enhanced dual inhibitory activity with selectivity fold of less than 30, UMB160 being the most potent dual-kinase bromodomain inhibitor (BRD4 IC50 = 28 nM, PLK1 IC50 = 40 nM). UMB131 was found to be the most selective PLK1 inhibitor over BRD4.

Keywords

cancer drugs, PLK1 inhibitors, BI-2536

Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

 
May 20th, 12:30 PM

Structural Activity Relationship Study on Dual PLK1 /BRD4 Inhibitor, BI- 2536

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 one target over the other. UMB101 and 160 have been found to exhibit enhanced dual inhibitory activity with selectivity fold of less than 30, UMB160 being the most potent dual-kinase bromodomain inhibitor (BRD4 IC50 = 28 nM, PLK1 IC50 = 40 nM). UMB131 was found to be the most selective PLK1 inhibitor over BRD4.

 

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