The Conrad Prebys Center for Chemical Genomics (CPCCG) at Sanford-Burnham Medical Research Institute is one of
four Comprehensive Screening Centers of the Molecular Libraries Probe Production Centers Network (MLPCN), the
production phase of the NIH’s 6-yr Molecular Libraries Program (MLP) that began on September 2, 2008
(https://mli.nih.gov/mli/). The CPCCG continues its mission to serve as a national resource through the MLPCN to speed
discovery of a basic research “toolbox” of potent, specific and selective small-molecule compounds (“probes”) that
modulate the activities of specific gene products in a desired manner, and thus allows interrogation cellular pathways in
greater depth. The MLP solicits Investigator initiated high-thoughput assays proposal for peer-reviewed competitive
funding. Awarded proposals are assigned to collaborate with one of the MLPCN centers for HTS execution, eventual
probe development and publication. The CPCCG has an active Outreach Program to educate the academic community
about the MLP and its grants; to navigate the application process and provide grant-writing resources; and to consult on
assay development and preliminary data generation.
The CPCCG can develop, implement, and execute virtually any biochemical or cell-based (including phenotypic, whole
organism, pathway and High Content Screening) high-throughput assays in workstation or fully-integrated modes. Our bicostal facilities in San Diego, California and Orlando, Florida house world class instrumentation and technology with
unparalleled flexibility and reconfigurability, that enables assays in almost every signal generation and detection
technology, and the complete infrastructure in tissue culture scale-up and maintenance, as well as protein production and
purification to support full production level frontline screening through to final target and compound prosecution. The
figure below summarizes CPCCG experience and capabilities with respect to target types and assay modalities. Since
the beginning of the MLPCN and its 3-yr pilot phase, CPCCG, has completed 76 HTS on the NIH’s full Molecular Libraries
Small Molecule Repository of compounds that now number 330,400 compounds, have delivered 32 new chemical probes
to the academic community, and uploaded 14.9 million datapoints to PubChem, the public chemical biological database
(http://pubchem.ncbi.nlm.nih.gov/)
In toto our current state-of-the-art robotic HTS
systems theoretically can process around >1
GPCR
million wells per day between a 1-PODfs HTS
system in San Diego and another 3-POD uHTS
system in Orlando. Complementary to the
molecular target approach, special mention
should be made of our automated microscopy
and full production High Content Screening (HCS)
systems and platforms which will facilitate the
analysis of pathways at the phenotypic level of gross (10-1000 micron) spatial (intracellular compartmentalization) and
temporal scale (minutes to hours) associated microscopic analysis of intracellular trafficking events. We are the only
MLPCN center that has completed any HCS (currently completed 11 HCS) projects. Additionally, we have individual
automated HT microscopes (Q3DM EIDAQ100 High-throughput Microscope for any format, including slides and 6 to 3456
wells, with CytoShop High-throughput Cell Analysis software) and three (3) production fully integrated HCS systems
based on the: 1)GE Amersham INCELL1000 HCS platform, 2) Beckman Coulter (Q3DM) IC100 and most recently, 3)
Perkin Elmer Opera™ HCS with on-board parallel processors and Acapella™ software for rapid real-time image
processing concurrent to image acquisition. A full listing of capabilities and specific instrumentation can be found on our
website (www.cpccg.burnham.org).
In addition to our HTS and high content screening (HCS) capabilities, we are currently the only center able to perform
NMR-based screens against targets for which no assay has been developed, and our biophysical and bioanalytical
validation team have access to very high-field nmr facilities (800 MHz) for both small molecule and protein nmr studies, as
well as micro-isothermal calorimetry to establish binding constants.
Finally, the CPCCG automated systems also support full rapid medium to high-throughput full dose response titrations, to
support a full medicinal chemistry and chemical informatics department with proven expertise and experience in hit-toprobe optimization through SAR development, directed chemical synthesis of analogs, along with full bioanalytical,
biophysical, computational, ADMET capabilities and exploratory pharmacology to support up to small animal PK/PD
dosing.