A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE

High Throughput Screening

High Throughput Screening Core
Mission
The High Throughput Screening (HTS) Core’s mission is to assist City of Hope researchers in identifying novel lead compounds for anticancer drug development and chemical probes useful for biochemical mechanistic studies via sophisticated high throughput screening assays of synthetic compound and natural product libraries.
 
A team of medicinal chemists, pharmacologists, structural biologists, bioinformaticians and clinicians contributes valuable input to optimize some of these small molecules for drug development and translate them into clinical evaluation in cancer patients. 
 
Compound Library
The core has a library of over 75,000 synthetic compounds that represent prime leads for drug development, as well as a library of over 7,000 natural product extracts comprising nearly 1 million individual compounds.
 
HTS Core Features Summary and Advantages
The HTS Core is a full-time, professionally-managed facility, boasting highly-trained and experienced staff, advanced equipment and a substantial compound library. These combined attributes and a centralized knowledge base increase cost effectiveness and productivity. Investigators also benefit from the cumulative experience gleaned from other projects in the High Throughput Screening Core.
 
Research reported in this publication included work performed in the High Throughput Screening (HTS) Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Interaction Between Cores

The following image shows interactions between the High Throughput Screening (green), Biomedical Informatics (yellow) and Synthetic and Biopolymer Chemistry (purple).
 
Experimental screenings performed in the Highthroughput ScreeningCore complement virtual screenings carried out by the Biomedical Informatics Core toward identifying “hits” for biomolecular targets of interest.
 
Confirmed hits, also known as leads, identified through screenings are used as starting points for chemists in the Synthetic and Biopolymer Chemistry Core for designing focused libraries. 
Molecular modeling expertise in the Biomedical Informatics Core aids the design process.
 
Chemists synthesize the focused libraries accordingly, which in turn are tested by high throughput screening.
 
Structure-activity relationship analysis is then carried out to evaluate newly synthesized compounds using appropriate in vitro or cell-based assays.
 
Iterative cycles of interactions of the three cores will speed up the “lead optimization” process and move the project forward.
 

Pricing

Prices and availability vary. Please Contact Us for current information.
 
If you are a City of Hope employee, please click herefor pricing.
 

Abstract

City of Hope researchers identify novel lead compounds for anticancer drug development and chemical probes useful for biochemical mechanistic studies via sophisticated high throughput screening (HTS) assays of synthetic compound and natural product libraries.
 
A team of medicinal chemists, pharmacologists, structural biologists, bioinformaticians and clinicians contributes valuable input to optimize some of these small molecules for drug development and translate them into clinical evaluation in cancer patients.
 
The HTS Core works closely with the Synthetic and Biopolymer Chemistry Core and the Biomedical Informatics Core in the identification, improvement and development of lead compounds, which in turn benefit chemical biology and drug discovery research at City of Hope.
 
The HTS Core facility occupies approximately 600 square feet of laboratory space in the newly-renovated Flower Research Building, which is five minutes from the main City of Hope campus. The lab has ample space for major robotic equipment, computers, freezers, a microplate washer and reader, tissue culture and benchtop working space. The core’s major equipment includes a Hudson Platecrane, a Beckman Biomek FX, a Tecan Ultra Plate Reader, a BioTek Elx405 Select Auto Plate Washer, a a Liconic Plate Incubator, Thermo Multidrop Micro, a Biacore T100 Surface Plasmon Resonance Biosensor and SoftLinx software.
 
The HTS Core is a full-time, professionally-managed facility, boasting highly-trained and experienced staff, advanced equipment and a substantial compound library. These combined attributes and a centralized knowledge base increase cost effectiveness and productivity. It would not be feasible or cost effective for individual investigators to acquire the necessary expertise and instruments to perform their own HTS. Investigators also benefit from the cumulative experience gleaned from other projects in the HTS Core.
 
The HTS Core has deployed a series of informatics programs and implemented standard operating procedures to ensure proper management of the large amount of information it handles regularly. These steps also foster efficient information exchange between the core and its users.

Equipment

The High Throughput Screening Core facility occupies approximately 600 square feet of laboratory space in the Flower Research Building, and contains major robotic equipment, computers, freezers, a microplate washer and reader, tissue culture and benchtop working space.
 
The major equipment is described in more detail below.
 
Programmable rotary robotic plate handler that shuffles microtiter plates between specified instrument positions and plate racks.
 
Beckman Biomek® FX
The Biomek FX Laboratory Workstation is a flexible, automated liquid handling system with a large work surface accommodating almost any highthroughput job size. The system comes configured with both 96-channel and Span-8 multichannel pipetting capabilities, simplifying highthroughput automation in 96- or 384-well format, with up to a 240-plate capacity with the Stacker Carousel. Multichannel pipetting makes for rapid compound transfer and addition of reagents. Automated labware positioners allow the researcher to customize the work surface with automated functionality such as shaking, stirring, heating and cooling for a given application; the integrated gripper frees the user from routine tasks like clearing the work surface to make room for more plates. An automated tip loader and Stacker Carousel storage likewise automate the routine task of providing disposable labware to the highthroughput system. The Biomek FX software is easy to use and possesses features for precise and accurate pipetting, as well as automation tools such as the Software Wizard, making it simple to write methods to automate any task.
 
Overlord™
Special supervisory software that allows the control of multiple instruments from one PC, Overlord operates in Windows 2000/XP environments with an easy-to-use drag-and-drop interface. Overlord utilizes the native software of ancillary equipment for maximum flexibility. Even the most complex system is easy to program and the most complex instrumentation is easy to integrate. There are over 300 Overlord installations in the field. Device drivers for Overlord are available for more than 300 instruments, and we use it to integrate the six instruments listed here into a screening platform.
 
Tecan ULTRA Plate Reader
Microplate reader capable of handling all fluorescence, luminescence, absorbance, fluorescence polarization and time-resolved fluorescence detection technologies.
 
In addition to managing detection technologies similar to those handled by Tecan Ultra, PHERAstar is equipped to handle the bead-based Amplified Luminescent Proximity Homogeneous Assay (AlphaScreen) technology patented by PerkinElmer.
 
BioTek Elx405™ Select Auto Plate Washer
A plate washer that is capable of washing 96- and 384-well microtiter plates. Users can adjust the flow rate, the dispense/aspiration volume and angle for applications from basic ELISA to cell washings.
 
LiCONiC Plate Incubator
Integrated incubator to allow screening with cell-based assays.
 
Thermo Multidrop Micro
Multidrop Micro is a high-speed 1-µl bulk reagent dispenser that precisely delivers microvolumes of 1-50 µl into 384- and 96-well microplates. It is especially useful forhigh throughput screeningassays set up with rare and/or expensive components.
 
Biacore T100 Surface Plasmon Resonance (SPR) Biosensor
State-of-the-art instrument for characterizing specific interactions of protein with other molecules such as proteins, synthetic and natural chemicals. The rates at which these molecules interact (binding and dissociation), and theiraffinity(how tightly they bind to another molecule) can be obtained easily.
 

Future Plans

Large-scale Protein Expression
Having sufficient quantities of reagents is a basic prerequisite to successful high-throughput screening (HTS). Often, supplies of target proteins are limited because most academic labs do not have the capability to produce the necessary amount of proteins. We plan to consult with the experts in City of Hope’s Center for Biomedicine & Genetics to establish large-scale protein expression capability to improve the protein supply bottleneck.
 
Addition of High Content Screening (HCS) Capability
Carrying out highthroughput cell-based “phenotypic” screening (HCS) requires integrated instrumentation and informatics infrastructures. These include automated digital microscopy, image analysis and data mining software, as well as a data management package. These infrastructures allow researchers to measure multiple end points/parameters simultaneously for every sample. They can then use advanced algorithms to dissect and distill useful information from the complex data set. We believe HCS capability will advance drug discovery on multiple fronts, including target identification and validation, primary and secondary screening, compound profiling and lead optimization.
 
Development of In Silico ADME Prediction and In Vitro ADME Testing
One of the major obstacles in drug discovery and development is the high failure rate of compounds during clinical trials. Many of the compounds fail because of poor absorption, distribution, metabolization and excretion (ADME) properties. With the advancement of computational power and methodologies, it is now possible to performin silicocalculation of a number of important ADME properties including aqueous solubility, log P octane/water, Caco-2 cell permeability and human serum albumin binding. By combining thein silicocalculation within vitroADME testing to confirm the predicted values, we can more accurately target selection of lead compounds for further development. The Biomedical Informatics Core will purchase ADME prediction software and make it available through City of Hope’s intranet. The HTS Core will establishin vitroADME assays, including Biomimetic Artificial Membrane Permeation Assay (BAMPA), Transil Human Serum Albumin (HSA) Binding Assay and Cytochrome P450 Isoenzymes Assay, to obtain experimental data on key ADME properties for compounds of interest.

Quality Control

By setting up the High Throughput Screening Core (HTS) in-house, we can provide timely assistance to City of Hope investigators regarding HTS assays development, validation and implementation. This allows for centralized quality control of drug screening and development. In addition, the HTS Core works closely with the Synthetic and Biopolymer Chemistry Core and the Biomedical Informatics Core in identifying, improving and developing lead compounds, which in turn benefit chemical biology and drug discovery research at City of Hope.
 
The HTS Core has deployed a series of informatics programs and implemented standard operating procedures to ensure proper management of the large amount of information it handles regularly. These steps also foster efficient information exchange between the core and its users.

 
Laboratory Information Management System
The HTS Core has set up a centralized database, built upon the Laboratory Information Management System developed by Cheminnovation called Chemical and Biological Information System (CBIS).
 
CBIS provides a Web-based application for managing chemical and biological materials and data throughout different cores and laboratory scientists, enabling insights resulting from high-volume data mining.
 
CBIS is hosted on the Biomedical Informatics Core’s high-availability Dell PowerEdge 2950, two dual-core 64-bit Xeon servers with 4GB RAM each and 1-terabyte SAN network storage space. CBIS’s integrated open framework of Web solutions has a user-friendly front end that can incorporate many external data mining applications and transparently link to relational database back end solutions.
 
Compound Registration
All compounds, regardless of source, are entered into the database and assigned a unique ID number, which facilitates tracking of the compound as it passes through various assays and tests.
 
Barcoding
All HTS assay plates use barcodes to allow tracking of the plates and data as compounds are tested in different assays.
 
Documentation
Reproducibility and robustness of each HTS assay is documented, e.g. by Z-factor analysis.
 
Statistical Analysis
S-PLUSsoftware, from Insightful Inc., is an industry-standard solution for exploratory data modeling and statistical analysis. With over 4,000 data analysis functions, including the most comprehensive and robust set of modern methods, S-PLUS is used on all data to ensure its quality and significance.
 
Information Exchange/Sharing
All high quality data is deposited into the central database in a timely manner to facilitate information exchange/sharing and discussions among researchers.

Services

A diagram showing processes within the HTS core.
The High Throughput Screening (HTS) Core facility offers the following services:
 
Consultation
Discussing with investigators the various approaches in identifying/screening compounds
 
Assay Development
Assisting investigators in developing new assays or adapting their low throughput assays into automated, high throughput screening formats. Assays may involve proteins, cell lines, or simple model organisms.
 
Assay Implementation
The core subjects the assays to high throughput screening and analyzes the results to identify active hits for each assay.
 
Data Analysis
Performing structure-activity relationship (SAR) analysis of compounds demonstrating activity in the individual assays.
 
Data Integration and Management
The core assists in collecting, maintaining and interpreting data for project investigators.
 
Drug Discovery: A Team Approach
Drug discovery is a multi-disciplinary effort. In order to advance a project efficiently, it is important that everyone involved be up-to-date with the progress of the project such as the latest hits/leads. It is also crucial to form a consensus about the characteristics of the compounds, e.g. potency, selectivity, etc., so that the team can effectively decide whether to go further with a particular compound and/or its derivatives. The HTS Core services provide an effective framework for the project team members to interact.
 
TheCore Advisory Committeerepresents the broad spectrum of expertise required for the successful operation of the HTS Core. This committee reviews all submitted proposals and ranks them based on their scientific merits and feasibility. Priorities are assigned to each proposal, and core staff members carry out the experiments accordingly. Highest priority is given to cancer center members with peer-reviewed funding.
 
Research Shared Services

City of Hope embodies the spirit of scientific collaboration by sharing services and core facilities with colleagues here and around the world.
 

Recognized nationwide for its innovative biomedical research, City of Hope's Beckman Research Institute is home to some of the most tenacious and creative minds in science.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.
Learn more about City of Hope's institutional distinctions, breakthrough innovations and collaborations.
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 
Media Inquiries/Social Media

For media inquiries contact:

Dominique Grignetti
800-888-5323
dgrignetti@coh.org

 

For sponsorships inquiries please contact:

Stefanie Sprester
213-241-7160
ssprester@coh.org

Christine Nassr
213-241-7112
cnassr@coh.org

 
CONNECT WITH US
Facebook  Twitter  YouTube  Blog
 
NEWS & UPDATES
  • Cancer cells may be known for their uncontrollable growth and spread, but they also differ from normal tissue in another manner: how they produce energy. In healthy cells, energy is derived primarily from aerobic respiration, an oxygen-requiring process that extracts the maximum possible energy from glucose, or...
  • Clinical trials are expensive and complex, but they’re essential for bringing new therapies to patients. Edward Newman, Ph.D., associate professor of molecular pharmacology, just boosted City of Hope’s ability to conduct those studies with a five-year, $4.2 million grant from the National Cancer Institute...
  • Meet City of Hope’s new chair of the Department of Surgery – esteemed pancreatic and hepatobiliary surgeon, researcher and author Yuman Fong, M.D. As one of today’s most respected and recognizable physicians in the treatment of cancers of the liver, bile duct, gallbladder and pancreas, Fong has pioneered and en...
  • For most of her life, Southern California teenager Kayla Saikaly described herself as healthy, even very healthy. She played basketball. She never missed school with as much as a fever. Her worst childhood illness was nothing more than a cold. Then, when she was 13, her nose started bleeding after a basketball ...
  • Neuroblastoma is one of the deadliest childhood cancers, accounting for 15 percent of pediatric cancer deaths. For patients with high-risk neuroblastomas, the five-year survival rate is 40 to 50 percent even with the most rigorous treatments available today. But those odds may improve soon, thanks to a new comp...
  • For breast cancer survivors, a common worry is a recurrence of their cancer. Currently, these patients are screened with regular mammograms, but there’s no way to tell who is more likely to have a recurrence and who is fully cleared of her cancer. A new blood test – reported in Cancer Research, a journal of the...
  • Metastasis — the spreading of cancer cells from a primary tumor site to other parts of the body — generally leads to poorer outcomes for patients, so oncologists and researchers are constantly seeking new ways to detect and thwart this malicious process. Now City of Hope researchers may have identified a substa...
  • Deodorant, plastic bottles, grilled foods, artificial sweeteners, soy products … Do any of these products really cause cancer? With so many cancer myths and urban legends out there, why not ask the experts? They can debunk cancer myths while sharing cancer facts that matter, such as risk factors, preventi...
  • Cancer risk varies by ethnicity, as does the risk of cancer-related death. But the size of those differences can be surprising, highlighting the health disparities that exist among various ethnic groups in the United States. Both cancer incidence and death rates for men are highest among African-Americans, acco...
  • George Winston, known worldwide for his impressionistic, genre-defying music, considers music to be his first language, and admits he often stumbles over words – especially when he attempts languages other than English. There’s one German phrase he’s determined to perfect, however: danke schön. Winston thinks h...
  • Few decisions are more important than those involving health care, and few decisions can have such lasting impact, not only on oneself but on relatives and loved ones. Those choices, especially, should be made in advance – carefully, deliberately, free of pain and stress, and with much weighing of values and pr...
  • Using a card game to make decisions about health care, especially as those decisions relate to the end of life, would seem to be a poor idea. It isn’t. The GoWish Game makes those overwhelming, but all-important decisions not just easy, but natural. On each card of the 36-card deck is listed what seriously ill,...
  • Young adults and adolescents with cancer face unique challenges both during their treatment and afterward. Not only are therapies for children and older adults not always appropriate for them, they also must come to terms with the disease and treatment’s impact on their relationships, finances, school or ...
  • Breast cancer is the most common cancer, other than skin cancer, among women in the United States. It’s also the second-leading cause of cancer death, behind lung cancer. In the past several years, various task force recommendations and studies have questioned the benefits of broad screening guidelines fo...
  • Paternal age and the health effects it has on potential offspring have been the focus of many studies, but few have examined the effect parental age has on the risk of adult-onset hormone-related cancers (breast cancer, ovarian cancer and endometrial cancer). A team of City of Hope researchers, lead by Yani Lu,...