Study of successful drug targets could hasten development of new m...(nds of less desirable targets To fi...)

To find out, the researchers looked at the relationships between 919 successful drugs, their human gene or protein targets, and the functional properties of those targets.

They found that most successful drugs are very precise; 62% of them have only one specific target.

But that's just a start. "A target molecule with an appropriate, 'drugable' structure is a necessary but not sufficient condition for success," write the authors. But the selection of a prospective drug target is "a complicated balance of many considerations,"

Additional properties that distinguish most good targets include:

• Connectivity--how many other proteins does the target protein interact with directly" Effective drugs targets--according to Rzhetsky and colleague Lixia Yao, from Columbia University--interact with about nine other genes or proteins, which is above average but not extremely high. This is enough connections to have a significant impact but not so many as to multiply the risks of serious side effects. The very-high-revenue drugs, the authors note, tend to target genes and proteins with slightly lower connectivity.

• Betweenness--how often does this protein serve as the shortest path between two networks of proteins" Successful drugs, they found, tend to bridge two of more clusters of interacting molecules.

• Consistency--how much does the gene for this protein vary from person to person" Limited individual variation is better, so the drug works the same way in most people.

• Tissue specificity--where is the gene for the drug target expressed" In just one tissue, say brain, or skin, or all over the body" Ideally, the researchers found that the best targets were genes or proteins primarily expressed in one specific tissue, so the drug treats the disease at its core, without interfering with other, healthy tissues or organs, and thus causes
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