Themed collection Strategies for Cellular Target Identification of Natural Products

Daniel Romo and Jun Liu introduce the Natural Product Reports themed issue on ‘Strategies for cellular target identification of natural products’.

Target identification of new bioactive compounds has been achieved by both our direct and indirect approaches. Here, we highlight the utility of the latter approaches, MorphoBase and ChemProteoBase.

A description of the T7 phage biopanning procedure is provided with tips and advice suitable for setup in a chemistry laboratory.

This highlight focuses on our recent discoveries and chemical genetics approaches for bioactive microbial metabolites that target cancer cells, the cancer microenvironment, and cell membrane signalling. In addition, the development of two new platforms to identify the cellular targets of these molecules is also discussed.

The natural products FR901464, pladienolide, and herboxidiene were discovered as activators of reporter gene systems. They were later found to inhibit the spliceosome.

Outbreaks of cyclopic lambs during the 1950s led to the discovery of cyclopamine and new anticancer therapies.

Direct capture of drug–target complexes in situ by using affinity-based probes allows target identification of natural products and bioactive compounds, even if the binding is reversible with moderate affinity.

In this highlight we describe two case studies from our laboratory, involving the biomimetic syntheses and the biological mechanism elucidation of the bioactive oligomeric sesquiterpenoids, (+)-ainsliadimer A (4) and (−)-ainsliatrimer A (5).

This review focuses on chemical probes to identify the protein binding partners of natural products in living systems.

This review focuses on and reports case studies of the latest advances in target protein identification methods for label-free natural products. The integration of newly developed technologies will provide new insights and highlight the value of natural products for use as biological probes and new drug candidates.

This review describes the status of the photo-cross-linked small-molecule affinity matrix while providing a useful tutorial for academic and industrial chemical biologists who are involved or interested in drug target identification.

Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds.

Biologically active compounds induce phenotypic changes in target cells, which can be used to predict their modes of action. Such changes were initially detected by a visual inspection of images, while recent studies are based on high content analysis (HCA) methods using automated microscopy and analysis software.