Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products

TY - JOUR

T1 - Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products

AU - Kibble, Milla

AU - Saarinen, Niina

AU - Tang, Jing

AU - Wennerberg, Krister

AU - Mäkelä, Sari

AU - Aittokallio, Tero

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Covering: 2011 to 2014 It is widely accepted that drug discovery often requires a systems-level polypharmacology approach to tackle problems such as lack of efficacy and emerging resistance of single-targeted compounds. Network pharmacology approaches are increasingly being developed and applied to find new therapeutic opportunities and to re-purpose approved drugs. However, these recent advances have been relatively slow to be translated into the field of natural products. Here, we argue that a network pharmacology approach would enable an effective mapping of the yet unexplored target space of natural products, hence providing a systematic means to extend the druggable space of proteins implicated in various complex diseases. We give an overview of the key network pharmacology concepts and recent experimental-computational approaches that have been successfully applied to natural product research, including unbiased elucidation of mechanisms of action as well as systematic prediction of effective therapeutic combinations. We focus specifically on anticancer applications that use in vivo and in vitro functional phenotypic measurements, such as genome-wide transcriptomic response profiles, which enable a global modelling of the multi-target activity at the level of the biological pathways and interaction networks. We also provide representative examples of other disease applications, databases and tools as well as existing and emerging resources, which may prove useful for future natural product research. Finally, we offer our personal view of the current limitations, prospective developments and open questions in this exciting field.

AB - Covering: 2011 to 2014 It is widely accepted that drug discovery often requires a systems-level polypharmacology approach to tackle problems such as lack of efficacy and emerging resistance of single-targeted compounds. Network pharmacology approaches are increasingly being developed and applied to find new therapeutic opportunities and to re-purpose approved drugs. However, these recent advances have been relatively slow to be translated into the field of natural products. Here, we argue that a network pharmacology approach would enable an effective mapping of the yet unexplored target space of natural products, hence providing a systematic means to extend the druggable space of proteins implicated in various complex diseases. We give an overview of the key network pharmacology concepts and recent experimental-computational approaches that have been successfully applied to natural product research, including unbiased elucidation of mechanisms of action as well as systematic prediction of effective therapeutic combinations. We focus specifically on anticancer applications that use in vivo and in vitro functional phenotypic measurements, such as genome-wide transcriptomic response profiles, which enable a global modelling of the multi-target activity at the level of the biological pathways and interaction networks. We also provide representative examples of other disease applications, databases and tools as well as existing and emerging resources, which may prove useful for future natural product research. Finally, we offer our personal view of the current limitations, prospective developments and open questions in this exciting field.

KW - Biological Products/pharmacology

KW - Computational Biology

KW - Drug Discovery

KW - Humans

KW - Molecular Structure

U2 - 10.1039/c5np00005j

DO - 10.1039/c5np00005j

M3 - Review

C2 - 26030402

SN - 0265-0568

VL - 32

SP - 1249

EP - 1266

JO - Natural Product Reports

JF - Natural Product Reports

IS - 8

ER -