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Poster

Exploiting Polypharmacology in Precision Oncology: Identification of Differential Kinase Off-targets Among Clinical PARP Inhibitors

Rectangle Image
Poster

Exploiting Polypharmacology in Precision Oncology: Identification of Differential Kinase Off-targets Among Clinical PARP Inhibitors

A more comprehensive and systems-based approach to pharmacology is uncovering that drugs tend to bind to more than one target, a behaviour commonly referred to as polypharmacology with clinical implications that are still not well understood.1

The increasing availability of ligand-target interaction data in the public domain in resources such as canSAR2 enables the development of computational methods to predict polypharmacology, that are becoming a cost-effective means to uncover new targets of drugs. PARP inhibitors are a new class of targeted small-molecule cancer therapeutics that have shown unexplained differential effects in cellular models and clinical trials.3

Can we use computational methods to identify previously unknown off-targets of PARP inhibitors that can explain their observed differences?

References

(1) Jalencas X, Mestres J. On the origins of drug polypharmacology. Med. Chem. Commun.,4, 80-87 (2013).

(2) Tym JE, Mitsopoulos C, Coker EA, Razaz P, Schierz AC, Antolin AA, Al-Lazikani B. CanSAR: updated cancer research and drug discovery knowledgebase. Nucleic Acids Res. 44, D938-43 (2016).

(3) AntolĂ­n AA, Mestres J. Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors. Oncotarget. 5, 3023-8 (2014).


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