Small Molecule Compound Libraries
The KU-HTS 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 systems for high volume storage and retrieval of chemical compounds and biological samples in a cold, nitrogen purged environment at -20ºC and 10% oxygen. Nitrogen is pumped into the system to displace oxygen to reduce humidity and prevent hydration of DMSO samples. The Labstore is composed of robotic systems for internally managing samples, imaging devices including both a video camera and a high megapixel camera internally, a large -20º freezer storage area, a heated 30º storage area, computer controllers, user interfaces, external condensers, and sensors and alarms to alert and regulate safe temperatures and oxygen levels. The new high-resolution camera allows capture and instant reading of an entire rack of 384 individual 2-D bar-coded tubes with a single photo. The Labstore also includes a special module for cherry picking and rearrangement of 2-D bar-coded tubes from a 384-tube rack.
Library Details
The HTS ready assay can be used to screen the University of Kansas (KU)-HTS compound collection of ~ 427,469 compounds and a small interfering RNA (siRNA) library of 2,157 siRNA duplexes for use in target identification and validation. The KU-HTSL 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 KU library of compounds is optimized for structural diversity and drug-like properties. Cheminformatics analysis has shown presence of 61,980 unique scaffolds across the entire collection. All compound collections follow Lipinski's Rule of Five and have purity of >90%. Compounds have been selected to be non-reactive and numerous filters were used to filter out any compounds containing reactive and unstable undesirable groups such as esters, amides, acid chlorides, Michael acceptors, and poly-aromatics These KU-HTS libraries have been used extensively in screening various targets and have resulted in valuable hits.
Bioactives and FDA-Approved compounds
A collection of 15,835 bioactive compounds and drugs approved by 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 will ensure an accelerated drug development and optimization processes. The FDA approved drug library is part of KU-validation set and is also 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 KU-HTS small molecule library consists of 398,829 compounds from various sources:(1) ChemBridge: 143,736 compounds from DIVERSet-CL and the DIVERSet-EXP libraries (2)ChemDiv Library: 167,406 compounds from ChemDiv diversity, BFL (sp3 hybridized carbon scaffolds for PPI), CNS (blood brain barrier permeable), 3D BioDiversity, peptidomimetics and SpiroBridge collections. collections.(3) Life Chemicals Library (65,280 compounds from 15K Diversity and Life PS5 compound sets) (4) MayBridge Hit Finder Diversity (16,400 compounds) (4) Tim Tec: 5,960 compounds from Actiprobe 5K and anti-infective sets.(5) Stemgent 47 compounds that modulate stem cell proliferation and differentiation.
Natural products: A collection of 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.