Rational discovery of dual-indication multi-target PDE/Kinase inhibitor for precision anti-cancer therapy using structural systems pharmacology.

ABSTRACT: Many complex diseases such as cancer are associated with multiple pathological manifestations. Moreover, the therapeutics for their treatments often lead to serious side effects. Thus, it is needed to develop multi-indication therapeutics that can simultaneously target multiple clinical indications of interest and mitigate the side effects. However, conventional one-drug-one-gene drug discovery paradigm and emerging polypharmacology approach rarely tackle the challenge of multi-indication drug design. For the first time, we propose a one-drug-multi-target-multi-indication strategy. We develop a novel structural systems pharmacology platform 3D-REMAP that uses ligand binding site comparison and protein-ligand docking to augment sparse chemical genomics data for the machine learning model of

SUBMITTER: Lim H 

PROVIDER: S-EPMC6576746 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature