A guest post by Ellen Berg

Phenotypic assays are compound screening systems that focus on the modulation of a disease-linked phenotype in a target agnostic manner, in contrast to those centering on a specific protein (as is the case in target-based drug discovery). See The why and how of phenotypic small-molecule screens and Developing predictive assays: The phenotypic screening “rule of 3” for more information.

Here, we have compiled a list of selected chemical probes that are suitable for characterizing phenotypic screens. These probes represent the best of the best, covering a broad range of pathway and target mechanisms with probes that are potent and selective for their targets or target class. These select chemical probes also cover pathways that are of interest in phenotypic drug-discovery (PDD) campaigns. These probes are well known, and many are approved as drugs. The clinical link is a benefit, as results with these particular probes can be connected to clinical findings. All of the probes on this list have been tested in the BioMAP platform of human primary cell-based model systems and have been shown to be active and well-behaved across a wide range of concentrations.

We hope that the development of a standard set of probes for phenotypic screens will inspire a community and create wide acceptance of criteria for PDD assays. Characterizing PDD screens with this set of probes will help researchers more quickly deconvolute the mechanisms of any hits. More importantly, the results of testing and sharing these data will help us better understand disease biology. Your feedback on this special probe collection is welcome!

Email: contact@chemprobes.org

Compound (Mechanism)

GDC-0941 (PI3K Inhibitor)

JQ1 (BET Inhibitor)

Rapamycin (mTOR Inhibitor)

Tofacitinib (JAK Inhibitor)

VX-745 (p38 MAPK Inhibitor)

8-CPT-cAMP (PKA/PKG Activator)

Atorvastatin (HMG-CoA reductase Inhibitor)

Colchicine (Microtubule Inhibitor)

Concanamycin (V-type ATPase Inhibitor)

GF 109203X (PKC (c+n) Inhibitor)

Vorinostat (HDAC Inhibitor)

Oligomycin A (Mitochondrial Inhibitor)

Phorbol 12-myristate 13-acetate (PKC Activator)

Prednisolone (GR Agonist)

R(-) Rolipram (PDE IV Inhibitor)

Tacrolimus / FK-506 (Calcineurin Inhibitor)

Trametinib (MEK Inhibitor)

Phenotypic probes: a special-use case