Web-Based Tools for Polypharmacology Prediction

Drug promiscuity or polypharmacology is the ability of small molecules to interact with multiple protein targets simultaneously. In drug discovery, understanding the polypharmacology of potential drug molecules is crucial to improve their efficacy and safety, and to discover the new therapeutic potentials of existing drugs. Over the past decade, several computational methods have been developed to study the polypharmacology of small molecules, many of which are available as Web services. In this chapter, we review some of these Web tools focusing on ligand based approaches. We highlight in particular our recently developed polypharmacology browser (PPB) and its application for finding the side targets of a new inhibitor of the TRPV6 calcium channel

Engineering patient-on-a-chip models for personalized cancer medicine

Traditional in vitro and in vivo models typically used in cancer research have demonstrated a low predictive power for human response. This leads to high attrition rates of new drugs in clinical trials, which threaten cancer patient prognosis. Tremendous efforts have been directed towards the development of a new generation of highly predictable preclinical models capable to reproduce in vitro the biological complexity of the human body. Recent advances in nanotechnology and tissue engineering have enabled the development of predictive organs-on-a-chip models of cancer with advanced capabilities. These models can reproduce in  vitro the complex three-dimensional physiology and interactions that occur between organs and tissues in vivo, offering multiple advantages when compared to traditional models. Importantly, these models can be tailored to the biological complexity of individual cancer patients resulting into biomimetic and personalized cancer patient-on-a-chip platforms. The individualized models provide a more accurate and physiological environment to predict tumor progression on patients and their response to drugs. In this chapter, we describe the latest advances in the field of cancer patient-on-a-chip, and discuss about their main applications and current challenges. Overall, we anticipate that this new paradigm in cancer in vitro models may open up new avenues in the field of personalized â cancer â medicine, which may allow pharmaceutical companies to develop more efficient drugs, and clinicians to apply patient-specific therapies. The authors acknowledge the financial support from the European Union Framework Programme for Research and Innovation Horizon 2020 on Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies (FoReCaST) under grant agreement no. 668983. D.C. and S.C.K also acknowledge the support from the Portuguese Foundation for Science and Technology (FCT) under the scope of the project Modelling Cancer Metastasis into the Human Microcirculation System using a Multiorgan-on-a-Chip Approach (2MATCH) (02/SAICT/2017 – n° 028070) funded by the Programa Operacional Regional do Norte supported by FEDER. Conflicts of interest: none