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.

This research was funded by the People Program (Marie Curie Actions) of the 7th Framework Program of the European Union (FP7/2007−2013) under REA grant agreement no. 600388 (TECNIOspring program) (A.A.A.); the Agency of Business Competitiveness of the Government of Catalonia ACCIO (A.A.A.); the Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204735/Z/16/Z) (A.A.A.); and the Spanish Ministerio de Economia y Competitividad grant BIO2014-54404-R (J.M.).