Is the Quest for Signaling Bias Worth the Effort?

The question of whether signaling bias is a viable discovery strategy for drug therapy is discussed as a value proposition. On the positive side, bias is easily identified and quantified in simple in vitro functional assays with little resource expenditure. However, there are valid pharmacological reasons why these in vitro bias numbers may not accurately translate to in vivo therapeutic systems making the expectation of direct correspondence of in vitro bias to in vivo systems a problematic process. Presently, in vitro bias is used simply as a means to identify unique molecules to be advanced to more complex therapeutic assays but from this standpoint alone, the value proposition lies far to the positive. However, pharmacological attention needs to be given to the translational gap to reduce inevitable and costly attrition in biased molecule progression.