Designing transient binding drugs: a new concept for drug discovery.

A multitude of weak, or transient, biological interactions (dissociation constant: K(d)>microM), either working alone or in concert, occur frequently throughout biological systems. We are starting to appreciate their importance in complex biological networks. This realization has important implications to drug discovery as we can question the current paradigm of drug design to find the highest possible binders (drugs) to a given target (receptor). Development of transient drugs, defined by their binding to target, can be based on high-off-rates, multivalent approaches or multiple targets. Now, techniques are available to discover such drug candidates. The greatest problem yet to overcome is probably the mind-set of the individual researcher that weak binders are undesired and therefore of no benefit.