Lead series

In general, there are three milestones for the drug discovery process. The first is the identification of a verified hit series (primary activity in a related series of molecules), the second the determination of a lead series (series with primary activity and drug-like properties), and the third a clinical candidate (activity, positive pharmaceutical, and pharmacokinetic properties devoid of toxicity). An example... 

The reader should note that there is a fully comprehensive coverage of organogold chemistry up to the year 1980 in the Gmelin Handbook of Inorganic Chemistry,3 Apart from COMC (1982) and COMC (1995), later reviews are available in Encyclopedia of Inorganic Chemistry and in a monograph,5 as a compilation of preparative procedures in the two leading series oriented at synthetic chemistry,6 7 and as summaries of theoretical work.8,9... 

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. 

Irreversible CYP inhibition, especially when considered as a cause of chemically reactive metabolites, raises a number of issues that should be considered early in the drug discovery process. Careful evaluation of the structural features of the lead series as well as screening for MBIs early in the drug development process should guide series selection and optimization with the goal of avoiding the introduction of potentially risky moieties into new chemical entities. 

Receptor Novascreen Biosciences Corporation Focuses on optimizing lead series... 

If multiple HTS actives of the same chemical family are to some extent leadlike (vide infra), they become a lead series, that is, structures that are amenable for further chemistry optimization and exhibit favorable patent situation [18, 19]. Lead series are further queried and derivatized in order to derive analogs with the appropriate blend of pharmacodynamic and pharmacokinetic properties. 

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