The Therapeutics Platform empowers researchers in the Broad community to discover small-molecule probes (used to understand cell circuitry and disease biology) and small-molecule therapeutics (used to treat disease).
A central goal of chemical biology is to harness the power of synthetic organic chemistry to discover and to elucidate molecular pathways fundamental in cellular, developmental and disease biology. The creation and use of small molecules to probe the genome is a fertile area of research that facilitates the translation of biological insights into powerful new medicines. The Therapeutics Platform comprises scientists from a wide range of disciplines (chemistry, biology, computational science, software and automation engineering), innovating and working cooperatively towards these goals. The platform team works in an extraordinary research environment that has high-throughput research capabilities in organic synthesis and small-molecule screening. Informatics and computational analysis teams integrate these capabilities to enable collaborating researchers to design new experiments and members of the global research community to benefit from the resulting discoveries.
Because of our extensive experience in small molecule design, screening, and large data set analysis, we maintain an active and diverse small molecule pipeline. Visit the Small Molecule Probe Development page for detailed information on these projects, including project timelines and published results.
Platform activities involve the coordination of efforts emanating from three core areas:
Our chemists use modern organic synthesis in three phases of the platform's research. One team of chemists synthesizes a Broad Institute small-molecule screening collection. This team uses diversity-oriented synthesis to prepare compounds having the ability both to modulate nearly any aspect of human biology and to be optimized. The second team uses follow-up chemistry to optimize "hits" in small-molecule screens in order to develop small-molecule probes with high potency and specificity. The third team undertakes another significant and impacting challenge -- to convert "hits" to candidate small-molecule therapeutics, a key step in enabling human clinical investigations.
Our informatics team manages data collection and integration from chemical synthesis through screening and data analysis. Electronic lab notebooks and an analytical chemistry data warehouse capture critical information about the synthesis of compounds that are later used for screening. They also make these data available during the analysis of screening results. These tools facilitate a more comprehensive analysis of assay results that provides better biological understanding and leads to more informed decisions. Automated lab management systems enable high-throughput operation and improve data quality by eliminating error-prone manual processes. We make our data and analysis tools available to the global scientific community through the public database ChemBank.
Our small-molecule screening team, which has existed for over 10 years, has facilitated small-molecule screening projects for more than 140 different research groups throughout the U.S. and abroad. These scientists, in collaboration with automation engineers, have built and now operate unique automation systems for compound management and screening. These systems store and retrieve two unique small-molecule screening collections that together will comprise over 500,000 compounds. The facility provides the functionality and flexibility to perform a wide range of assays with extraordinary accuracy and production capacity. These assays include both target-based biochemical screens and cell-based phenotypic screens, using novel screening approaches (e.g., gene expression-based screening, high-content live-cell imaging, RNAi combined with small molecules) with relevance to disease areas including psychiatric disease, cancer, infectious disease, and diabetes.