Compound Libraries Available for High-Throughput Screening (HTS) in the Stanford HTSKC

Diverse Screening Collection (127.5K drug-like molecules):

The major diversity based libraries available for High-Throughput Screening in the HTBC are:

• ChemDiv (50K)
• SPECS (30K)
• Chembridge (23.5K)
• ChemRoutes (24K)
• We also have several sets of combinatorial/directed libraries (86.66K):
• Enamine-CNS Library (47.36K) molecules selected to be able to penetrate blood-brain barrier (BBB) (Only available to Stanford Researchers).
• ChemDiv Kinase (10K) (Mitotic Kinase targeted library info, Tyrosine Kinase targeted library info).
• ChemDiv Allosteric Kinase Inhibitor Library (26K)
• ChemDiv Sag/Hedgehog library (3300)
• Covalent libraries (21.12K only available to Stanford Researchers)
• Enamine Cysteine focused Covalent fragments (3200) 
• Enamine Lysine Covalent fragments (1600)
• Enamine Serine Hydrolase (12,160)
• Enamine  Serine Focused Covalent fragments (1600)
• Enamine Covalent Screening Chloroacetamides 2021 (1200)
• Enamine Covlaent fragments Chloroacetamides (1360)
•  

Known Bioactives and FDA Approved Drugs (11,272 Compounds): 

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--Not typically screened)
• Microsource Spectrum (2000 compounds)
• Biomol (now Enzo Life Sciences) ICCB Known Bioactives (480 compounds) and FDA Approved Drug Library (640 compounds)
• Selleckchem FDA approved drug library (3000 compounds)
• MedChemExpress drug library-custom (339 compounds)
• Internal Compounds from ChEM-H Medicinal Chemistry (933 compounds)

For more info on drug repurposing go to the Broad Drug Repurposing Hub or IRDiRC Drug Repurposing Guidebook: making better use of existing drugs to tackle rare diseases.

Compound Fragment Libraries (5K): 

For fragment screening (Surface Plasmon Resonance-SPR on a Biacore T200) in collaboration with the PAN facility, the HTBC has obtained 5000 compound fragments: How Library was generated

• Maybridge Ro3 Diversity Fragment Library (2500 compounds, Flyer)
• Life Chemicals Fragment Libraries (2500 compounds)
• The HTSKC screens one compound per well in a 384-well or 1536-well microplate format (744 X 384 well plates, 189 X 1536-well plates*), but can  be screened at several different concentrations (qHTS).
• PDF of list of Available Screening Compounds
• *Not including Covalent Libraries.

Online Tools: 

For Compound Re-orders search:

• eMolecules
• Zinc Express (paper) -- use converter below to get Zinc IDs
• iScienceSearch
• MolPort 
• PubChem 
• 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
• Experimental Strategies for High-Quality Hit Selection from Small-Molecule Screening Campaigns

Is your hit a promiscuous hit compound?

Check it here (Scripps), unfortunately site is no longer available.

Is your hit real? Review this paper and this one or this one, or this one, or this one, or this one, or this one (Nuisance compounds in Cellular Assays), or this one (The future of phenotypic drug discovery)

The You can also check it at Badapple or use the cAPP from the Hoffmann Lab

Also, Check our list of potential problem compounds in the HTBC library here.

Overview of how compounds were selected 

(Properties of current library Powerpoint PDF):

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 HTSKC's library.