Compound Libraries Available for High-Throughput Screening (HTS) in the Stanford HTBC
Our compound library contains over 130,000 diverse compounds
Diverse Screening Collection:
The major diversity based libraries available for High-Throughput Screening in the HTBC are:
- ChemDiv (50K)
- SPECS (30K)
- Chembridge (23.5K)
- We also have two sets of combinatorial/directed libraries:
- ChemRX (10K)-no longer screened
- ChemDiv Kinase (10K) (Mitotic Kinase targeted library info, Tyrosine Kinase targeted library info).
Known Bioactives and FDA Approved Drugs:
For assay validation, smaller screens, and drug repurposing screens we have libraries of known modulators/FDA approved drugs including;
- Library of Pharmacologically Active Compounds (LOPAC1280)
- NIH Clinical Collection (NIHCC) (446 compounds)
- NCI DTP (3084 compounds)
- Microsource Spectrum (2000 compounds)
- Biomol (now Enzo Life Sciences) ICCB Known Bioactives (480 compounds) and FDA Approved Drug Library (640 compounds)
For more info on drug repurposing go to the Broad Drug Repurposing Hub or the NIH Discovering New Therapeutic Uses for Exisiting Molecules.
Compound Fragment Libraries:
- Maybridge Ro3 Diversity Fragment Library (2500 compounds, Flyer)
- Life Chemicals Fragment Libraries (2500 compounds)
- The HTBC screens one compound per well in a 384-well microplate format (~500 384 well plates) except the LOPAC, Microsource and Biomol libraries which are screened in a 7 point titration (qHTS).
- MS Excel list of Available Screening Compounds
For Compound Re-orders search:
- SAR tool Scaffold Hunter
- Convert your ID to CID or other ID at CTD - The Chemical Translation service (UC Davis)
- Website with tons of links to online tools--Virtual Ligand Screening
Is your hit a promiscuous hit compound?
Check it here (Scripps), unfortunately site is no longer available.
Also, Check our list of potential problem compounds in the HTBC library here.
Overview of how compounds were selected
The initial 30,000 compounds from Specs were selected on the following criteria, with the help of Anang Shelat of R. Kip Guy's lab formerly at UCSF. Anang used InHouse models and the commercially available, Scitegic Pipeline Pilot, to perform the computational analysis. The 50,000 compounds from ChemDiv were selected similarly by Brian Wolff in collaboration with Jan Williams, formerly at the Small Molecule Discovery Center-HTS Division, and James Wells at UCSF. Additionally, we purchased a 10,000 compound Kinase-directed library from ChemDiv with funds from a generous donation by a private foundation. For additional information on screening compounds see PubChem.
(A) Using SD files (structure files containing over 200,000 compounds available) from Specs, molecules were passed through a standardization procedure: charges were cleared and set to formal charge, salts were stripped, certain topologies (such as nitro, sulfate) were canonicalized, and a canonical tautomer was selected.
(B) These molecules were passed through a Lipinski "Rule of Five" filter: Num_Atoms > 0 AND (N_count and O_count <= 10) AND (100 <= MW >= 500) AND (Num_H_Donors <= 5) AND (-5 <= AlogP <= 5) AND All Organic Atoms (salts were stripped earlier, so they are not considered here). This resulted in about 150,000 molecules.
(C) These modified Lipinski molecules were ionized using an InHouse pka model and filtered based on formal charge: -3 <= FC <= 3. Nearly all the molecules passed.
(D) The molecules were then passed through a REOS (Rapid Elimination of Swill) filter (eliminating functional groups deemed reactive by literature and consultations with medicinal chemists). This step eliminated another 30,000 molecules.
(E) A Bayesian categorizer was used to distinguish the Specs molecules from UCSF's InHouse Library (input variables: chemical fingerprint and calculable physical properties). The compounds from Specs were annotated with this score (), thus creating a diversity spread of the library. lower score = most unlike InHouse compounds
(F) A randomized selection of the ~120,000 compounds was ordered to comprise the initial 30,000 compounds of the HTBC's library.
- Christopher A. Lipinski, Franco Lombardo, Beryl W. Dominy, Paul J. Feeney "Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings", Adv. Drug Delivery Rev., 2001, 46(1-3), 3-26. PMID 11259830 .
- Brian Y. Feng, Anang Shelat, Thompson N. Doman, R. Kip Guy, & Brian K. Shoichet "High-throughput assays for promiscuous inhibitors", Nature Chemical Biology, 2005 Aug;1(3):146-8 .
- James Inglese, Douglas S. Auld, Ajit Jadhav, Ronald L. Johnson, Anton Simeonov, Adam Yasgar, Wei Zheng, and Christopher P. Austin "Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries", PNAS, 2006 Aug.1; 103(31):11473-11478.