This facility specializes in chemical biology as it relates to drug discovery, biological probe discovery, and phenotypic characterization of small-molecule effects on cellular and biochemical systems. In addition to housing the instrumentation and robotics required for High-throughput Screening (HTS), the Core houses cutting-edge High Content Screening (HCS) for next-generation small-molecule discovery research and analysis in fixed or live cells and cellular systems. In addition, we specialize in three-dimensional (3D) high content imaging and analysis.
The Core is designed as a resource for HTS/HCS of small-molecule compound libraries in any cellular or biochemical assay system. We currently have approximately 135,000 compounds available for screening. For a detailed summary of the steps in a typical screening campaign, please see HTS and HCS information and resources. In addition to small-molecule screening, the instrumentation in this facility is available on an hourly basis with nominal charges.
3-arm Janus Liquid Handling Robot
BioTek ELx405 Plate Washer
BioTek MultiFlo Bulk Liquid Dispenser
The EnVision is a multi-mode plate reader capable of collecting data for all common assay types on 96, 384, or 1536 well plates. This includes:
The EnVision can be run in stand-alone mode (useful in assay development or for small numbers of plates), or as an automated, integrated system with the Janus liquid handler (Useful for large screens).
FDA Approved Drug Library: 12,000 drugs with utility in drug repurposing. This library is provided by and maintained by the Colorado Clinical and Translational Sciences Institute (CCTSI), CU AMC.
Kinase Inhibitor Library: 875 compounds including clinically relevant or FDA approved kinase inhibitors.
Spectrum Collection: 2,320 compounds approved drugs (50%), diverse natural products (30%), and other bioactive compounds (20%).
Custom Drug-Like Diversity Sets (120,000 compounds): These libraries are intended for discovering drug-like molecules that can be translated into novel intellectual property. Inherent to these libraries are derivatives of chemical scaffolds, which can yield SAR (structure-activity relationship) that guide downstream medicinal chemistry efforts. These libraries have been filtered to remove undesirable compounds (e.g. PAINS)
A typical HTS campaign encompasses three main steps, outlined below. It is assumed that the general concept of the screening approach, as well as the possible assays involved, have been discussed between the PI and the HTS Director. It is also highly preferable, though not absolutely required, to have initial results and, if possible, a working assay in hand prior to initiating the screening effort. This enables the HTS lab to focus immediately on the first phase: Adaptation and statistical validation of the assay or screen.
Please click on the steps below for a detailed description.
The costs associated with HTS and HCS drug discovery as well as chemical biology are project specific and as a result, the costs will vary greatly on a per project basis. To obtain a detailed quote for your research project please contact Dan LaBarbera (Core Director) or Qiong Zhou (Core Lab Manager) to schedule a consultation. We can typically provide cost estimation after initial consultation within one week.
Notes on Authorship
Co-authorship is generally expected when core personnel have made significant contributions to the research in the form of consultation, experimental design, method development, data analysis and/or data interpretation. Significant is defined as “the project would not have progressed, or progressed at a substantially slower pace, without the guidance of facility personnel”. In such cases, core personnel should have the opportunity to review and edit manuscripts before submission.
Acknowledgment of facility contributions is expected in publications that include any data generated in the facility or using core instrumentation or software. An example of an appropriate acknowledgment is “The authors wish to thank the High-throughput Screening (HTS) Drug Discovery and Chemical Biology Core Facility at the University of Colorado Anschutz Medical Campus for their contributions to this manuscript”.
Please inform us when relevant publications are accepted, as we would like to post citations on our website. This information is vital to the continued support of the facility.
Grant Assistance and Percent Effort
We are very happy to provide letters of support and assistance in grant writing. For letters of support, please allow at least 2 weeks from the time of your request. Please furnish the following information: Title of grant, agency to which you are submitting the grant, your title and mailing address, and 1-3 sentences on the goals (or specific aims) of your proposal.
Our facility is also dependent on grant support for long-term success and we appreciate your support in keeping the facility funded. To determine if percent effort by core personnel is required, please consider the following: