Dual Inhibitors of PARPs and ROCKs
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 si...
| Autores: | , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/36571 |
| Acceso en línea: | http://hdl.handle.net/10230/36571 http://dx.doi.org/10.1021/acsomega.8b02337 |
| Access Level: | acceso abierto |
| Palabra clave: | Receptors cel·lulars Proteïnes |
| Sumario: | 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. |
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