Small Molecules
The Center has a collection of more than 140,000 compounds, including commercially-available as well as proprietary compounds. The collections include 4,200 known bioactive compounds (including those from the NIH bioactive compound set) and more than 500 Yale proprietary chemicals. Every compound purchased includes characterization data, including an LC/MS trace as well as a proton NMR spectrum, indicating compound purity and identity. Quality control analytical chemistry are performed on all hit molecules from screens, verifying purity and identity.
Maximal chemical diversity is achieved by acquisitions from multiple vendors (with virtually no overlap in chemical composition) and with libraries from distinct synthetic sources. Our libraries score well against typical Pharma “Diversity” collections and cover nearly identical chemical space.
Figure: The YCMD collection (red) compared in 18-dimensional descriptor space to a typical Pharma diversity set (purple). Chemical descriptors for 140,000 YCMD compounds were projected into 3D space using three principle components.
In addtion to insuring a wide-sampling of chemical diversity, the majority of YCMD compounds conform to rule-of-three and rule-of-five drug-likeness guidelines, providing compounds with good cellular permeability and drug-lead potential.
“Targeted” libraries are available, including:
- A “CNS library” composed of molecules with high blood-brain barrier permeability.
- Kinase inhibitor libraries
- Epigenetic libraries composed of molecules with a high likelihood of perturbing epigenetic mechanisms
In addition to the pre-arrayed subsets of the library above, custom subsets can be acquired pooled or unpooled, in various plate formats (contact YCMD staff for further information).
More detail may be found on our Small-molecule Subsets page.
siRNA
The siGenome collection is a human full genome library consisting of roughly 18,119 genes arrayed in 58 384-well plates with columns 1, 2, 23 and 24 empty and thus eligible for control testing. Each sample well contains a pool of 4 different siRNA targeting the same gene. Clients can choose to screen the full genome library or the following subsets of the library:
The full genome library is made up of the following subsets:
Druggable Genome (9 plates - 2,739 genes) Download gene list
(ion channels, proteases, phosphatases, kinases, ubiquitin conjugation proteins, and G-protein coupled receptors)
Drug Targets (15 plates - 4,795 genes) Download gene list
(genes involved in apoptosis, senescence, nucleic acid binding, autophagy, DNA repair, and characterized nuclear receptors, potential therapeutic targets)
Human Genome (34 plates - 10,582 genes) Download gene list
(genes not contained in other subsets including uncharacterized genes)
Please contact Janie Merkel (janie.merkel@yale.edu) for the current per assay plate fee structure applicable to your project. All compound plates have the same per assay plate fee structure.
Natural Products
The Center collaborates with various Yale faculty members engaged in natural products research to prepare extracts from a variety of sources. These complex extracts are plated out at a known concentration in 384 well plates and are made available for screening free of charge. Active wells are then put through subsequent steps of bio-assay guided chromatographic fractionation to begin the process of identification of active components.