Screening compounds

The KU High Throughput Screening Laboratory has a Universal Labstore from Nexus Biosystems, funded by a grant from the Kansas Biosciences Authority. The Labstore is a large 590-cubic-foot compound storage system, occupying over 73-square-feet of floor space. The Labstore is a laboratory system for high-volume storage and retrieval of chemical compounds and biological samples in a cold, nitrogen purged environment at 20 degrees below zero Celsius and 10% oxygen. Nitrogen is pumped into the system to displace oxygen to reduce humidity and prevent hydration of DMSO samples.

KU-HTS compound libraries

The HTS ready assay can be used to screen our compound collection of about 411,200 compounds and a small interfering RNA (siRNA) library of 2,157 siRNA duplexes for use in target identification and validation. Our collection of small organic molecules was carefully selected from several of these commercial vendors, targeting successful identification of lead compounds for use in screening projects. The compound library is optimized for structural diversity and drug-like properties. Cheminformatics analysis has shown the presence of > 61,980 unique scaffolds across the entire collection. All compound collections follow Lipinski's Rule of Five and have purity of more than 90%. We have selected non-reactive compounds and used numerous filters to eliminate any compounds containing reactive and unstable undesirable groups, such as esters, amides, acid chlorides, Michael acceptors, and poly-aromatics. These libraries have been used extensively in screening various targets and have resulted in valuable hits.

Bioactives and FDA-approved compounds:

We house a collection of 16,079 bioactive compounds and drugs approved by the FDA assembled from Selleck Chemicals, Prestwick Library, MicroSource Spectrum Library, Sigma LOPAC, Enzo, TimTec and BioFocus NIH clinical collection. The collection also includes 96 drug compounds licensed by Pfizer (Selleck Pfizer licensed compound library).  All of the FDA-approved compounds have well-characterized bioactivity, safety and bioavailability and hits from this set of compounds, ensuring an accelerated drug development and optimization processes. The FDA-approved drug library is part of a KU-validation set and is well-suited for drug repositioning for use in novel indications. The drug repurposing set is an annotated set of structurally diverse and cell permeable peptides, inhibitors, natural products and chemotherapeutic agents that are known to impact diverse signaling pathways and covers all major drug target classes. The compounds are carefully selected for their structural diversity, broad spectrum activity covering several therapeutic areas — from neuropsychiatry to cardiology, immunology, anti-inflammatory, analgesia and more — and for their known safety and bioavailability profiles in humans.

Diversity sets:

The small-molecule library consists of 380,897 compounds from various sources:

• ChemBridge: 100,000 compounds from DIVERSet-CL and the DIVERSet-EXP libraries
• ChemDiv Library: 146,265 compounds from ChemDiv Diversity, BFL (sp3 hybridized carbon scaffolds for PPI), CNS (blood brain barrier permeable), 3D BioDiversity, Peptidomimetic Soluble Diversity and SpiroBridge collections
• Life Chemicals Library: 103,725 compounds from 15K Diversity, PS4, 3DShape, Fsp3 and PS5 compound sets
• MedChemExpress Epigenetics Library, 1325 compounds
• MedChemExpress Immunology/ Inflammation Library, 5006 compounds.
• MayBridge Hit Finder Diversity: 16,400 compounds
• Tim Tec: 5,960 compounds from Actiprobe 5K and Anti-infective sets
• Stem cell Library: 1562 compounds that modulate stem cell proliferation and differentiation

Natural products:

Purified 12,805 natural products from Analyticon, GreenPharma and Life chemicals. Compounds like amino acids, peptides, nucleic acids, long fatty chains, metals were discarded, and different phytochemical families were selected carefully in order to have as much family representatives as possible.