Drug Discovery, Development and Delivery Core Facility (D4 Core)
About the D4 Core Facility
The D4 core is a collaboration involving many on-site facilities such as the organic synthesis core for drug development and hit-to-lead optimization and the imaging core for nanotech drug delivery characterizations.
We are a conveniently located, centralized facility providing a one-stop shop to fully realize your drug's potential.
Benefits of the D4 Core:
- High-throughput screening of chemical libraries or developing drug delivery formulations (i.e. nanotechnology).
- 101,680 independent compounds available for personalized drug screening.
- Potential to discover chemical agents that affect cellular targets involved in human diseases.
- Increased opportunities for successful grant funding.
- Avoid high cost and time investment needed to train lab personnel
- Technical expertise and infrastructure to support activities from automation aspects of screening to finding pre-clinical candidates.
The Drug, Discovery, Development and Delivery Core have available a total of 101,680 small molecule compounds available for screening from its commercially purchased libraries.
Small Molecule Library: The DIVERSet library collection from Chembridge offers a diverse set of 100,000 drug-like compounds with extensive pharmacophore coverage for primary screening. Stringent chemical group filters, coupled with a 3D conformer analysis, were used in selecting this set to provide maximum. More than 670 scientific articles that cite ChemBridge libraries or compounds have been published in premier journals, such as Science, Nature Cell Biology, JACS, PNAS, JBC, and Cancer Research.
FDA-Approved Library: Our newest addition includes the Prestwick Chemical Library, which contains 1200 small molecules that are 100% FDA approved drugs, presenting the greatest possible degree of drug-likeliness. The active compounds were selected for their high chemical and pharmacological diversity, as well as for their known bioavailability and safety in humans. The compounds in this library contain highly diverse drug molecules for which bioavailability and toxicity studies have already been performed and which have proven usefulness in humans. This library was designed to reduce the risk of low quality hits, reduce the cost of the initial screening, and accelerate lead discovery.
Natural Product Library: The core also has available a 480 compound natural product library from TimTec. This library is composed of naturally derived products from plant, animal and fungal sources and natural compounds including but not limited to, alkaloids, natural phenols, nucleoside analogs, carbohydrates, purines, pyrimidines, flavonoids, steroidal compounds and natural amino acids.
OSC Proprietary Library: Medicinal chemists of Organic Synthesis Core (OSC) have over the years developed their own chemical library that includes more than 100 chemicals. These are novel compounds synthesized in the Core lab and little is known about their mechanisms of action. The library includes class of compounds that have shown efficacy as inhibitors of Akt pathway, HDAC, Rho kinase, sphingosine kinase, Cox-2, Mcl-1, and Sirt-1 etc. based on the limited studies performed on them till date.
Molecular Devices FlexStation3: Capable of doing fluorescence, absorbance, and luminescence, time resolved fluorescence, and fluorescent polarization, as well as endpoint, kinetic, and spectrum reads. The flex unit allows addition of reagents to the wells immediately before reading the wells allowing us to do assays such as flash luminescence
Integra VIAFLO 96/384: This enables transfers of 96 and 384 samples in a single step, thus increasing pipetting throughput and reproducibility significantly. This type of robot operates at a fraction of the cost of most liquid handling platforms and can be used in manual, assisted and fully automatic modes. While it is not a “program and walk away” robot, it has the advantage of being highly flexible and adaptive to changes in the assay.
Eppendorf epMotion 5070 liquid handling robot: For dispensing the chemical library for assays and adding reagents required for the assay. The epMotion has a wide range of capabilities including but not limited to performing dilution series, repeat pipetting, delivery of as little as 1 uL of sample, transfer of reagents from tubs, microcentrifuge tubes, 96 and 384 well plates to the destination plates.
GE Biacore 3000: Used in measuring protein-protein interaction and binding affinity. The technology is based on surface plasmon resonance (SPR), an optical phenomenon that enables detection of unlabeled interactants in real time. The SPR-based biosensors can be used in determination of active concentration as well as characterization of molecular interactions in terms of both affinity and chemical kinetics.
Malvern Zetasizer ZS90: Measurement of particle size and molecular size at a 90 degree scattering angle using Dynamic Light Scattering, also with the ability to measure zeta potential and electrophoretic mobility using Laser Doppler Microelectrophoresis, and molecular weight using Static Light Scattering. Size measurement from 0.3nm (diameter) to 5 microns, zeta potential of colloids and nanoparticles using patented M3-PALS technology, molecular weight measurement down to 9,800Da, and 21CFR part 11 software compliant.
Seahorse XFe Extracellular Flux Analyzer: Measurement of metabolic assays. Simultaneously measuring the two major energy producing pathways of the cell – mitochondrial respiration and glycolysis – in a microplate, in real-time. This fast and sensitive measurement of cellular bioenergetics is label-free, enabling time-resolved analysis and the reuse of the cells. XF assays provide increased throughput in a drug discovery format that is superior to its single parameter predecessors.
We are in the Main Building on the south side in room C2705, adjacent to the Institute of Personalized Medicine.
Please contact us at 717-531-4172 to arrange a consult or tour of our facility.
Director: Dr. Kent Vrana, Ph.D.
Lab Manager: Adam Beck
Research Technologist: Patricia Mantero