**1. Introduction**

In the last decade, the interdisciplinary field of chemical biology has emerged from the need to better understand the role of proteins or signaling pathways in cellular systems and whole organisms than it was previously feasible with more classical genetic tools or methods. Rather than changing the levels of proteins, or blocking completely their expression or activity, by deleting or overexpressing their respective DNA or RNA sequences, it is now becoming more and more possible to precisely modulate their function in a time- and concentration-dependent manner using potent, selective and cell-permeable chemical compounds. Although the relevance of these so-called chemical tool compounds or probes for solving basic mechanistical questions in life sciences is indisputable [1], their role often extends into the fields of pharmacology and molecular medicine. In fact, chemical tools are playing an important role in the validation of newly identified drug targets in pharmaceutical companies, and might even serve as starting points for the development of new therapeutics.

Despite recent technological advances in areas such as cryo-electron microscopy (Cryo-EM) [2], the major approach for identifying bioactive substances is still the systematic testing of compound collections, often comprising many thousands or

even millions of individual substances, with target- or pathway-specific biological assays which are designed to produce reproducible biological activities with high signal-to-noise ratios under experimental conditions which are fast, miniaturized and therefore cost-effective [3]. This approach is technically and logistically challenging and, in the past, could only be performed by large pharmaceutical companies. In addition to experienced personnel, it requires large facilities with often expensive equipment for compound storage, automated liquid handling and sensitive detection of biological reactions. In recent years, however, this picture started to change. In the wake of the sequencing of the human genome, mostly larger academic institutions started to create their own screening and translational drug discovery centers because many new potential drug targets were suddenly becoming available for which a solid understanding of their physiological roles and molecular mechanisms were missing. At the same time, pharmaceutical companies faced increased pressures due to high drug development costs, often resulting in down-sized research budgets and cost cutting exercises combined with a general trend of becoming risk-averse towards innovative drug targets with potential high failure rates [4]. As a result, many experienced industrial 'drug hunters' found employment in academic chemical probe discovery centers, supporting their efforts and helping to alleviate some of the initial issues these centers faced [5].

In this chapter we describe some of these new initiatives which were created to develop chemical tool compounds outside of the traditional pharmaceutical industry, highlighting their particular strengths, challenges and access models for the mostly academic scientific community.
