Lead optimization approaches

BACKGROUND AND OBJECTIVES OF SAFETY LEAD OPTIMIZATION APPROACHES... 

Having said all this, a recent report from a major pharmaceutical company with one of the largest reported screening collections revealed that just over 50% of their current lead optimization efforts invoke a "fast follower" approach [114]. Why is this One might speculate that as most companies work on the same targets these days chemists find it easier to "patent bust" than wait for the results of an HTS campaign which may take months to develop. Possibly, when more novel targets are identified, HTS of enhanced collections will deliver upon the promise that they hold. 

Fig. 103 shows all scenario profits in the one-phase and the two-phase optimization case as well as the sales quantity index the two-phase optimization results do not disperse as strong as the one-phase-optimization. Besides, the worst case scenario is comparably better than the worst case scenario of the one-phase-optimization strategy. The plan is more cautious supply quantities are reduced leading to lower expected profits but better minimum profits in the worst case scenario. Although robustness is not measured it get s visible in the numerical tests for the 2-phase optimization approach. 

An early identification of the best leads is critical, and systematic biological profiling, as with Cerep BioPrint , enables this progress to a great extent. Experience with using this approach in a major pharmaceutical company (Pfizer) has confirmed this. One component of the issue can be stated that it is better to identify the best (not just potency) lead series than to try and find the best candidate from a possibly suboptimal series, which can happen at late stages of lead optimization, where it is very difficult to make major changes to the lead series chemistry. 

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