Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum

Well-characterized small molecules are essential tools
for studying
the biology and therapeutic relevance of a target protein. However,
many compounds reported in the literature and routinely studied in
biomedical research lack the potency and selectivity required for
mechanistic cellular studies on the function of a given protein. Furthermore,
commercially available compounds often do not include useful tools
developed by industry as part of their research and development efforts,
as they frequently remain proprietary. The freely available donated
chemical probe (DCP) library, fueled by generous donations of compounds
from industry and academia, enables easy access to a steadily growing
collection of these valuable and well-characterized tools. Here, we
provide a systematic description of the current DCP library collection
and their associated comprehensive characterization data, including
a variety of in vitro and cellular assays. Of note,
we characterized the set in relevant human primary models by employing
hepatotoxicity screening in primary human liver spheroids and viability
screening in patient-derived colorectal cancer organoids and matched
normal-adjacent epithelium. Taken together, the DCP library represents
a well-annotated, openly available collection of tool compounds for
studying a wide range of targets, including kinases, G-protein-coupled
receptors, and ion channels. As such, it represents a unique resource
for the biomedical research community.