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ACS Omega. 2018 Oct 31;3(10):12707-12712. doi: 10.1021/acsomega.8b02337. Epub 2018 Oct 5.

Dual Inhibitors of PARPs and ROCKs.

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Research Group on Systems Pharmacology, Research Program on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.


Recent network and system biology analyses suggest that most complex diseases are regulated by robust and highly interconnected pathways that could be better modulated by small molecules binding to multiple biological targets. These pieces of evidence recently led to devote efforts on identifying single chemical entities that bind to two different disease-relevant targets. Here, we first predicted in silico and later confirmed in vitro that UPF 1069, a known bioactive poly(ADP-ribose) polymerase-1/2 (PARP1/2) molecule, and hydroxyfasudil, a known bioactive Rho-associated protein kinase-1/2 (ROCK1/2) molecule, have low-micromolar cross-affinity for ROCK1/2 and PARP1/2, respectively. These molecules can now be regarded as chemical seeds from which pharmacological tools could be generated to study the impact of dual inhibition of PARPs and ROCKs in preclinical models of a variety of complex diseases where both targets are involved.

Conflict of interest statement

The authors declare the following competing financial interest(s): J.M. is the founder of Chemotargets S.L., the company that develops the Chemotargets CLARITY platform.

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