Pharmaceutical properties lead candidate

A qualitative process approach to accelerated development emphasizes the elimination of drug candidates from the pipeline. This approach targets the advanced evaluation of specific pharmaceutical properties. The reward is not necessarily intuitive introduce a qualitative process change earlier in the drug development pipeline, resulting in the proactive identification of promising lead compounds and the utilization of fewer resources during the costly clinical development phases. This approach is driven by kinetic ... 

The success of the pharmaceutical industry depends largely on the synthesis and screening of novel chemical entities and their ability to optimize selected leads into marketable drugs. In a market where development costs are exceptionally high, the ability to shorten optimization times would be desirable to reduce this cost. Furthermore, new technology that would enable a cost-effective upward step-change in the number of lead candidates that could be prepared would provide an obvious competitive advantage, as this would potentially enable the discovery of a better lead with enhanced therapeutic properties, with reduced side effects. 

At this moment the attrition rate in clinical trials is far too high. If, better-quality candidates are developed in preclinical research, the likelihood that they will pass the clinical trials will be increased. The cost savings in such a, case will be enormous. A recent study has revealed that more than 40% of the candidates in clinical trials fail due to poor (bio)pharmaceutical properties and more than 20% due to toxicity. These reasons depend heavily on the chemistry of the candidate and probably could be identified in preclinical research. The rate-limiting aspect of drug discovery is not in finding the lead it is turning the... 

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... 

A lead is variously defined in the pharmaceutical industry as a compound derived from a hit with some degree of in vitro optimization (potency in primary assay, activity in functional and/or cellular assay), optimization of physical properties (solubility, permeability), and optimization of in vitro ADME properties (microsomal stability, CYP inhibition). Moreover, a lead must have established SAR/SPR around these parameters such that continued optimization appears possible. A lead may also have preliminary PK and in vivo animal model data. However, it is the task of the lead optimization chemist to improve PK and in vivo activity to the levels needed for identification of a clinical candidate. 

High-throughput drug-like property profiling is increasingly used during lead identification and candidate selection. HTS pharmaceutical profiling may include ... 

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