DCI acquired equipment and a library of ~800,000 compounds from the Sanford Burnham Prebys Medical Discovery Institute in 2018. DCI’s capabilities include
Assay development / assay implementation
Ultra high-throughput screening (uHTS)
In Silico Modelling and Docking
Analysis, design, metabolism, excretion, and toxicology studies (ADMET)
Computational chemistry/Computer Aided Drug Design (CADD)
DCI has partnered with Alchem Laboratories Corporation (Alchem-DCI) for discovery and screening of compounds. Alchem-DCI can rapidly identify active compounds that modulate biomolecular pathways and other assays in 384 or 1536 well plates. The Alchem-DCI screening facility currently houses all of the NIH Molecular Libraries compounds (current size is ~370,000), as well as a collection obtained from Sanford Burnham Prebys Medical Discovery Institute, which contains approximately 420,000 synthetic small-molecule compounds, totaling a complete library of approximately 800,000 unique compounds in-house. The Alchem-DCI uHTS screening facility holds a library of stock plates, whose contents are catalogued in our biological database from Cheminnovation Software Inc. Assay plates for screens are created by acoustically transferring nanoliter quantities of compounds from the wells of a stock plate to the corresponding wells of an assay plate. A carousel system is used to store assay plates for high storage capacity and high-speed access. Three integrated robots transport assay microplates from station to station for sample and reagent addition, mixing, incubation, and finally readout or detection. The uHTS system can prepare, incubate, and analyze many plates simultaneously, further speeding the data-collection process. Depending on the assay the uHTS robots can test on average approximately 100,000 compounds per 8 hour / day. The “hits” generated by results from assaying compounds are cherry picked and then re-run in the screening assay as well as orthogonal or selectivity assays to reconfirm and narrow down the hit set. Typically, the initial screening hits display binding affinities for their biological target in the micromolar (2-10 µM) range.
Hit to lead (H2L), also known as lead generation, is a stage where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO). The drug discovery process generally follows target validation (TV), assay development, high-throughput screening, hit to lead (H2L), lead optimization (LO), preclinical drug development, and clinical drug development.
