**2. Developing chemical probes in academic networks**

At the beginning of the 21st century, academic institutions first began to implement dedicated assay development and screening centers which were soon followed by reports on the systematic testing of small molecule compound libraries in the US [6]. Comparable efforts in Europe's research institutes immediately received much attention, fostering collaborations between chemistry and biology groups and the establishment of academic screening platforms of diverse size. However, single platforms alone could not support comprehensively the needs of academic or industrial users due to limited chemical diversity of their compound collections and/or limited technical capabilities, and big pharma platforms were at that time not open to academic users. Pooling and coordination of public resources and expertise became imperative. Therefore, the efforts in the US were replicated with similar initiatives in countries such as France (Chimiothèque Nationale), Germany (ChemBioNet), Spain (ChemBioBank) and several others. Some years later, long-term cooperations between academic centers from different countries as well as public-private partnerships were established. We will describe some of these initiatives in more detail and will put particular emphasis on the collaborative model of the youngest organization for chemical biology, the EU-OPENSCREEN ERIC.

#### **2.1 The molecular libraries program (MLP) in the US**

The large, NIH-funded MLP was created in 2004 with the ambitious goal of creating a small molecule probe for every human protein in order to define the functions of genes, cells, and whole organisms in health and disease. The three components of the initiative were essentially: (a) a network of comprehensive and specialized screening centers plus specialized chemistry centers, (b) several cheminformatics approaches which included also a newly created

**115**

*Accelerating Chemical Tool Discovery by Academic Collaborative Models*

**2.2 The chemical biology consortium Sweden (CBCS)**

public compound database called PubChem with assay metadata, and (c) initiatives to generally advance technologies in the fields of chemical diversity, assay development and screening [6]. The aim was always to publish the new chemical probes and associated data immediately so that compounds could be used by the academic scientific community not only for basic research questions, but also for mechanistic validation of potentially disease-relevant drug targets and drug

Individual scientists could apply for funding to the NIH for their assay development and screening projects. Successfully, peer-reviewed projects were taken on board by one of the MLP centers, and high-throughput screens were conducted with a library which, by the end of the program, consisted of 390.000 compounds. About 5% of these molecules with often novel scaffolds were delivered by the academic synthetic chemistry community. In many cases, further chemical optimization yielded probes against protein targets which were deemed challenging or even 'undruggable'. Overall, during the 10-year period of the program, a total of 375 chemical tool compounds were developed against a broad range of target classes. 18 of these compounds were considered sufficiently interesting to serve as starting points for the development of therapeutics against a total of eight disease targets or target classes, and were licensed to biotech and pharmaceutical companies [7]. In light of the investment into the MLP it is debatable whether the ratio of probes to drug candidates can be regarded as a success or a disappointment but it certainly highlights the difficulties that chemical biologists are facing when they want to keep up with the speed of biological discoveries while translating academic findings into

Although much smaller than the MLP in the US, this example of a national consortium can highlight very well the particular strengths of a focused organization with only a few members. CBCS, with two nodes at the Karolinska Institutet and Umeå University, was founded as a non-for-profit research infrastructure for chemical biology in 2010 [8] by researchers from Biovitrum (former Pharmacia and Upjohn) and became an integrated platform of SciLifeLab, an already existing national centre for molecular biosciences, in 2013 [9]. The combined platform can investigate both chemical and genetic perturbations in biological systems. CBCS wants to enable high level basic research with open access publications while at the same time linking up academic and industrial groups. Complementary to CBCS, SciLifeLab offers a dedicated platform for drug discovery and development, with the clear goal of accelerating projects with translational potential. After nearly 10 years of operation, the consortium has produced more than 130 co-authored publications and 11 patent applications while scientific data provided the basis of

Users are encouraged to discuss in more detail project proposals with the CBCS staff prior to the submission of the official application. A proposal template, user agreements and estimated costs of typical screening and chemistry projects are available online. Project proposals are evaluated by an independent 'Project Review Committee' (PRC), which meets biannually. Prioritized projects may be subsidized, with the remaining costs covered by the applicant. Implemented projects are periodically re-evaluated by the Project Review Committee as they progress to pre-defined milestones. A project plan for a so-called "large collaborative project" may run over a maximum of 2 years for which the user is expected to cover the costs for all reagents and consumables, including a compound access fee for plating of library compounds.

There are also "small collaborative projects" which involve only limited CBCS

*DOI: http://dx.doi.org/10.5772/intechopen.91138*

development.

therapeutics.

six start-up companies [10].

#### *Accelerating Chemical Tool Discovery by Academic Collaborative Models DOI: http://dx.doi.org/10.5772/intechopen.91138*

*Cheminformatics and Its Applications*

mostly academic scientific community.

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].

**2. Developing chemical probes in academic networks**

organization for chemical biology, the EU-OPENSCREEN ERIC.

The large, NIH-funded MLP was created in 2004 with the ambitious goal of creating a small molecule probe for every human protein in order to define the functions of genes, cells, and whole organisms in health and disease. The three components of the initiative were essentially: (a) a network of comprehensive and specialized screening centers plus specialized chemistry centers, (b) several cheminformatics approaches which included also a newly created

**2.1 The molecular libraries program (MLP) in the US**

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

At the beginning of the 21st century, academic institutions first began to implement dedicated assay development and screening centers which were soon followed by reports on the systematic testing of small molecule compound libraries in the US [6]. Comparable efforts in Europe's research institutes immediately received much attention, fostering collaborations between chemistry and biology groups and the establishment of academic screening platforms of diverse size. However, single platforms alone could not support comprehensively the needs of academic or industrial users due to limited chemical diversity of their compound collections and/or limited technical capabilities, and big pharma platforms were at that time not open to academic users. Pooling and coordination of public resources and expertise became imperative. Therefore, the efforts in the US were replicated with similar initiatives in countries such as France (Chimiothèque Nationale), Germany (ChemBioNet), Spain (ChemBioBank) and several others. Some years later, long-term cooperations between academic centers from different countries as well as public-private partnerships were established. We will describe some of these initiatives in more detail and will put particular emphasis on the collaborative model of the youngest

**114**

public compound database called PubChem with assay metadata, and (c) initiatives to generally advance technologies in the fields of chemical diversity, assay development and screening [6]. The aim was always to publish the new chemical probes and associated data immediately so that compounds could be used by the academic scientific community not only for basic research questions, but also for mechanistic validation of potentially disease-relevant drug targets and drug development.

Individual scientists could apply for funding to the NIH for their assay development and screening projects. Successfully, peer-reviewed projects were taken on board by one of the MLP centers, and high-throughput screens were conducted with a library which, by the end of the program, consisted of 390.000 compounds. About 5% of these molecules with often novel scaffolds were delivered by the academic synthetic chemistry community. In many cases, further chemical optimization yielded probes against protein targets which were deemed challenging or even 'undruggable'. Overall, during the 10-year period of the program, a total of 375 chemical tool compounds were developed against a broad range of target classes. 18 of these compounds were considered sufficiently interesting to serve as starting points for the development of therapeutics against a total of eight disease targets or target classes, and were licensed to biotech and pharmaceutical companies [7]. In light of the investment into the MLP it is debatable whether the ratio of probes to drug candidates can be regarded as a success or a disappointment but it certainly highlights the difficulties that chemical biologists are facing when they want to keep up with the speed of biological discoveries while translating academic findings into therapeutics.
