Small Molecules, Big Players: the National Cancer Institute's Initiative for Chemical Genetics

Abstract

In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the crossfertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank. broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings. (Cancer Res 2006; 66(18): 8935-42)

A Cell-Based High-Throughput Screen Validates the Plasmodial Surface Anion Channel As an Antimalarial Target

“…Identification of a Diverse Collection of Inhibitors. We then used the optimized assay to execute a high-throughput screen of approximately 70,000 compounds from commercial, synthetic, and natural product libraries under an investigator-initiated open access facility at the Broad Institute (Tolliday et al, 2006). Each compound was tested at a 10 M final concentration along with DMSO alone control wells in each screening plate.…”

“…Although some hits were from natural product libraries and may contain mixtures of compounds with unknown structures, many hits were from commercial libraries with high purity and known structures. Additional hits came from the Broad Institute's in-house diversity-oriented syntheses (Tolliday et al, 2006). Starting with compounds having known structures, we selected 16 compounds available for secondary evaluation and obtained a 100% retest rate using cuvette-based osmotic lysis experiments in our National Institute of Allergy and Infectious Diseases laboratory.…”

Targeting the Human Cancer Pathway Protein Interaction Network by Structural Genomics

“…Our structure-function database can be leveraged by many other related initiatives. For example, the National Cancer Institute's Initiative for Chemical Genetics aims to systematically identify perturbational small molecules for each cancer-related protein coded in the human genome (84). Our structural genomics efforts on HCPIN will provide biochemical and structural information as well as key reagents, organized at a single Website, beneficial for such chemical genetics studies (85).…”

Chemical Biology/ Chemical Genetics/ Chemical Genomics: Importance of Chemical Library

“…They also emphasize its significance in human diseases quoting, "Chemical diversity provides a powerful tool to probe biological systems, as well as to discover new diagnostics and therapies for human disease." Stuart Schreiber has assigned 3 tasks to the Chemical Biology Platform at Broad Institute; the first is to be a DOS-oriented chemical library provider, the second is to perform HTS using highly sophisticated assay equipments and detection systems, and the third is to establish and operate a bioinformatics deposit center (ChemBank [15].…”