Donated chemical probes for open science

Abstract

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project.

Phenotypic Screening Combined with Machine Learning for Efficient Identification of Breast Cancer-Selective Therapeutic Targets

“…However, the power of predictability of idTRAX is limited by the compound set used for the training and how well the inhibitors can discriminate between different kinases. For that reason, it is important to develop even better sets of well-profiled inhibitors with broader target ranges and higher level of selectivity and it is promising that such efforts are moving ahead (Drewry et al, 2017;Muller et al, 2018). We are also putting our efforts in compilation of a high-quality consistent database for drug target interaction which we call Drug Target Commons (https:// drugtargetcommons.fimm.fi) (Tang et al, 2018), this kind of extensive dataset will definitely serve better for target deconvolution approaches.…”

Polycomb/Trithorax Antagonism: Cellular Memory in Stem Cell Fate and Function

“…The realization that PcG and TrxG proteins play critical roles in cancer prompted the development of small molecules that inhibit their functions (Helin and Dhanak, 2013;M€ uller et al, 2018). Such ''epigenetic drugs'' or ''epi-drugs'' that reversibly modulate enzymatic activities or protein interactions of specific PcG and TrxG family members are generally considered more amenable to clinical applications than therapeutic strategies based on genome alterations.…”

Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

“…No longer are we solely reliant on natural product inhibitors of epigenetic regulators, which often lack selectivity. Exhaustive and sophisticated medicinal chemistry programs in industry and academia have led to the development of highly selective and potent inhibitors of a wide array of epigenetic targets, and many of the compounds are available to the scientific community through programs such as the Structural Genomics Consortium 30 . Coupling the use of these compounds with well-validated phenotypic assays, such as cell-based assays of cardiomyocyte hypertrophy or fibrosis 31 , has the potential to rapidly uncover novel roles for epigenetic regulators in the control of heart failure and thus provide crucial mechanistic insights.…”