On the Organization of a Drug Discovery Platform

Abstract

Some of the most exciting parts of work in the pharmaceutical industry are the steps leading up to drug discovery. This process can be oversimplified by describing it as a screening campaign involving the systematic testing of many compounds in a test relevant to a given pathology. This naïve description takes place without taking into consideration the numerous key steps that led up to the screening or the steps that might follow. The present chapter describes this whole process as it was conducted in our company during our early drug discovery activities. First, the purpose of the procedures is described and rationalized. Next follows a series of mostly published examples from our own work illustrating the various steps of the process from cloning to biophysics, including expression systems and membrane-bound protein purifications. We believe that what is described here presents an example of how pharmaceutical industry research can organize its platform(s) when the goal is to find and qualify a new preclinical drug candidate using cutting-edge technologies and a lot of hard work.

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

“…The main ones are in our opinion: the way diseases can be simplified-or not-to a molecular target that is amenable to HTS; the choices of the molecules which can be screened into these assays; the quality of the assays and/or their sensitivity; the statistical considerations to determine the threshold at which a compound is recognized as an active; and finally, the source of the screened molecules. We (Boutin et al, 2018) and others (Schmid et al, 1999;Dufresne, 2000;Thiericke, 2000;Mayr and Bojanic, 2009;Bodle et al, 2017) exposed our screening strategies at several occasions, and considering the diversity of the potential problems, it can be hard to identify a universal approach. This is a fact that HTS promising techniques have not delivered as many drugs as expected with regard to the price and the ambition of the solutions/organizations involved (Newman and Cragg, 2016).…”

Industrial and academic approaches to the search for alternative melatonin receptor ligands: An historical survey

“…We documented the necessities for such task in the past, in the melatonin domain, 33 and outside of it. 34…”

“…This approach permitted to run many assays in standard, robotic formats, leading to strong numerous data. 34…”

“…A brief and evident shopping list of what is needed to conduct such a task—finding new ligand(s) at a receptor—will follow. We documented the necessities for such task in the past, in the melatonin domain, 33 and outside of it 34 …”

“…That is, with a miniaturization and automation of the assay in a 96‐ and then in a 384‐well plate formats. This approach permitted to run many assays in standard, robotic formats, leading to strong numerous data 34 …”