Take 2: What Protein And Where It Is Located Are Important For Drug Design

The research is published Feb. 23, 2009, in the Journal of Clinical Investigation.

The authors developed small molecules, which they termed Gamitrinibs, that target Hsp90, a protein that controls the folding of proteins in multiple signaling networks that drive tumor development and progression. In addition to targeting a protein that controls multiple signaling pathways, the authors designed the drugs to target one specific cellular compartment in which Hsp90 is active in tumor cells, mitochondria. Importantly, treatment with these drugs effectively induced tumor cell death in mice transplanted with human tumor cell lines.

The authors therefore conclude that combinatorial drug design, whereby inhibitors of signaling networks are targeted to specific cellular compartments, may prove a more effective strategy for developing anticancer drugs than targeting single signaling pathways.

In an accompanying commentary, Nesrin Özören and colleagues, at Bogaziçi University, Turkey, highlight the novelty and clinical potential of this approach.