1. Academic Validation
  2. Development of small-molecule probes that selectively kill cells induced to express mutant RAS

Development of small-molecule probes that selectively kill cells induced to express mutant RAS

  • Bioorg Med Chem Lett. 2012 Feb 15;22(4):1822-6. doi: 10.1016/j.bmcl.2011.09.047.
Michel Weïwer 1 Joshua A Bittker Timothy A Lewis Kenichi Shimada Wan Seok Yang Lawrence MacPherson Sivaraman Dandapani Michelle Palmer Brent R Stockwell Stuart L Schreiber Benito Munoz
Affiliations

Affiliation

  • 1 The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, United States.
Abstract

Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against Cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRAS(G12V) followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRAS(G12V) oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML162 and CID 49766530, ML210) with nanomolar potencies and 4-23-fold selectivities, which can potentially be used for identifying oncogene-specific pathways and targets in Cancer cells.

Figures
Products