Screening Compounds

The KU-HTS laboratory has a 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.

KU-HTS Compound Libraries

The HTS ready assay can be used to screen the University of Kansas (KU)-HTS compound collection of ~ 300,000 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. 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. Cheminformatics analysis has shown presence of 61,980 unique scaffolds across the entire collection. These KU-HTS libraries have been used extensively in screening various targets and have resulted in valuable hits.

Bioactives and FDA-Approved compounds:

Selleck Bioactives (http://www.selleckchem.com/screening/chemical-library), a collection of 1900 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.

Sigma LOPAC collection: A set of 1280 biologically annotated collection of inhibitors, receptor ligands, pharma-developed tools, and approved drugs impacts impacts most signaling pathways and covers all major drug target classes.

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 100,000 compounds from DIVERSet-CL and the DIVERSet-EXP libraries from the ChemBridge Corp. (San Diego, CA). 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.

ChemDiv Beyond the Flatland (33,864 compounds) sp3 hybridized carbon scaffolds, for targeting protein-protein interactions.

ChemDiv CNS set (26,136 compounds), compounds that can cross blood-brain barrier.

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.

Natural product-like Library (Life Chemicals Inc.): A collection of 8128 compunds with likeness to bioactve natural product scaffolds, that are amenble to chemcial synthesis.

MayBridge HitFinder: A collection of 14,400 compounds representing drug-like diversity, selected using standrad Daylight Fingerprints with the Tanimoto similarity index clustering at 0.71 similarity.  All compounds fit Lipinski's Rule of Five and have purity of >90%. Compounds have been selected to be non-reactive, ensuring fewer false positives and higher quality results.

MayBridge Mini Hitfinder:A collection of 2000 diverse compounds randomly selected from Maybridge HitFinder.

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

TimTec Anti-Infectives Library : includes 960 low molecular weight, drug-like molecules with scaffolds found in antiseptic agents with anti-bacterial (Gram+ve and Gram-ve), anti-fungoid, anti-microbial activities.

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.

 

NIH-CoBRE-funded Libraries:

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 5126 compounds have drug-like characteristics and pharmacological activity based on established drug design principles. (NIH CCET CoBRE funding: 8P30GM103495)

Analyticon Natural products library:  A colleciton of 4196 compounds, purified (>85%) compounds isolated from plants (MEGxp) and microorganisms (MEGxm).(NIGMS Chemical Biology of Infectious Disease grant P20GM113117 03)

ChemDiv Peptidomimetics library: A collection of 12,139 organic molecules that mimic the activity of peptides, a relatively unexplored area with a high potential of obtaining hits.(NIGMS Chemical Biology of Infectious Disease grant P20GM113117 03)

ChemDiv 3D Biodiversity: A collection of 19,528 scaffolds identified from the 3D clustered biologically annotated chemical space.(NIGMS Chemical Biology of Infectious Disease grant P20GM113117 03)