Screening Compounds

The KU-compound library collection is stored in the Universal Labstore from Nexus Biosystems, funded by a grant from the Kansas Biosciences Authority (KBA). 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.

The Nexus Labstore stores compounds across 5,616 plates in 384-well format, for a maximum capacity of 2,156,544 wells, with the option of quadrupling this storage with the use of 1,536-well plates. The Nexus Labstore is very flexible, with the ability to hold plates, tubes, and dram vials. Its shelves can hold either 5,616 SBS-footprint plates or 74,880 dram vials, or any combination of the two, as the system intelligently sorts and defragments the shelves to maximize storage capacity. A benefit of the system is its modular nature of the system fits well with our growing needs, as it can be upgraded with new stations, storage units, and modules in the future.

Compound Libraries

The compound library at KU-HTSL includes over 229,000 diverse compounds, a growing collection of over 1000 natural products, 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. In addition to using the Lipinski rule in the selection process, the HTS core also drew upon the vast drug discovery experience of professors in the KU Dept. of Medicinal Chemistry in selecting these compounds. The KU library of compounds is optimized for structural diversity and drug-like properties.

Bioactives and FDA-Approved compounds:

Selleck Bioactives (http://www.selleckchem.com/screening/chemical-library), a collection of 1835 structurally diverse and cell permeable bioactive compounds and peptides which include inhibitors, natural products and chemotherapeutic agents.

FDA Approved Drugs: KU-HTS has assembled a collection of bioactive drugs approved by FDA and which are currently in clinical use. The KU-HTS  assembled FDA drug collection derived from Prestwick and Microsource, Enzo, TimTec, Selleck, 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.

Prestwick Library: The Prestwick Chemical's (Illkirch, France) library is a unique collection of 1120 off-patent small organic molecules, 90% being marketed drugs and 10% bioactive alkaloids or related substances. 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.

MicroSource Spectrum Library: The 2000 compounds from the Spectrum collection of MicroSource Discovery Systems, Inc. (Gaylordsville, CT) encompass a wide range of biological activities and structural diversity for screening programs. The collection contains drugs from three sources: (1) US drug collection of 1040 drugs that have reached clinical trial stages in the USA. Each compound has been assigned USAN or USP status and is included in the USP Dictionary the authorized list of established names for drugs in the USA(2) an International Drug Collection of 240 drugs that are marketed in Europe and/or Asia (3) the rest is a unique collection of pure natural products and their derivatives.Natural Products include simple and complex oxygen heterocycles, alkaloids, sequiterpenes, diterpenes, pentercyclic triterpenes, sterols, and many other diverse representatives.

Diversity Sets:

ChemBridge Library: A collection of 43,736 compounds from ChemBridge Corp. (San Diego, CA) was selected from the Express-Pick collection of 450,000 compounds. Reactive, unstable and potentially toxic compounds, such as esters, amides, acid chlorides, Michael acceptors, and poly-aromatics were eliminated, and all compounds are solids with molecular weight between 150 and 480 and cLogP below 5. This is a library of compounds that was optimized for structural diversity and drug-like properties.

ChemDiv Library: A library of 56,232 compounds were purchased from ChemDiv, Inc.(San Diego, CA). The ChemDiv compounds have distinct properties and structural scaffolds compared to the ChemBridge compounds.

Life Chemicals Library: The library is a collection of 15,000 unique compounds representing 1717 unique scaffolds  from Life Chemicals library. Numerous filters were used to select scaffolds iincluding Lipinski's rule of five as well as filtering out any compounds containing more than 60 undesirable scaffolds.

TimTec Actiprobe 5K: ActiProbe Series provides access to some of the most diverse chemotypes among distinctly drug-like molecules available from TimTec extended stock. 

KU-CMLD Collection: The University Of Kansas Center Of Excellence in Chemical Methodologies & Library Development (KU CMLD) has synthesized libraries utilizing new principles of scaffold design. The compounds have drug-like characteristics and pharmacological activity based on established drug design principles.

Natural Products (GreenPharma): A collection of 480 purified, chemically diverse and drug-like compounds, a subset of much larger 150,000 natural compound structures. 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

KU Legacy compound collection: The legacy library is includes a very valuable collection of more than 200 compounds synthesized by KU Medicinal chemists.