Lead discovery process

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Because polypeptides are involved in many regulatory processes in the body, polypeptides and their analogues are natural drug candidates. Endogenous polypeptides tend to be very potent with strong binding. Therefore, a known polypeptide is essentially already a lead, and the entire lead discovery process can be skipped. 

A pivotal feature of the preclinical lead discovery process for identifying orally active platinum complexes was a comparison of antitumor activity in mice bearing the ADJ/PC6 subcutaneous murine plasmacytoma by the oral vs. intraperitoneal (i.p.) routes of administration. The ADJ/PC6 tumor model had been widely used in earlier platinum drug development pro-... 

Statistical HTS data analysis and discovery cheminformatics are integral components of an HTS-driven lead discovery process. Various statistical and visualization techniques are routinely... 

However, the promise of major improvements in productivity, cost efficiency, and speed of discovery has created radical changes in the way drug discovery is carried out. Leading this wave of change has been the development and implementation of a series of innovative, state-of-the-art technologies aimed at the early lead discovery process. 

At this point in the lead discovery process, there are a number of significant compound selection choices that depend on target knowledge and/or the ligands that bind to the target. Some of these choices can be relatively straightforward. 

Afto ordering a copy of the compound deck in the plate format of choice, the screening process can be carried out very rapidly (a matter of weeks). The screening scientist monitors the automated system continuously for both hardware and assay performance. Of all the different stages in the lead discovery process, the actual screening is now the quickest. 

Fig. 16-1 From target identification to optimization process is performed in cycles, candidate drug (CD). Target identification and at the end of the lead optimization and validation are followed by lead discovery process the developability of the and lead optimization. The lead compounds is traditionally investigated.

As discussed and schematically shown in Figure 1.4.3 the lead discovery process is divided in several phases. In the very early phase of hit identification, where a large number of compounds are screened in the HTS, libraries usually consist of randomly selected compound collections where the structural and chemical diversity should be as large and random as possible. 

---