1.2.1. Introduction to drug discovery. Prediscovery of targets

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In past, research into new drugs was accomplished in a very different way to today. Many of these drugs were simple homemade remedies, which were passed on from generation to generation and most of them discovered by accident. This is the case for one of the most famous antibiotics ever: penicillin. 
In 1928, Alexander Fleming observed that a staphylococcus bacteria culture that he was studying was
contaminated by a certain fungus (penicillium) and that the area around these fungi was free from bacteria. It was later on, Howard Floyd who realised the tremendous potential of penicillin for wounded soldiers during the II World War.
Although these kinds of discoveries still occur today, they are not as usual as they used to be and tend to have less impact than penicillin had at the time. Currently a much more methodical process is followed which involves industry, universities, government agencies and even philanthropic organisations. The development of drugs begins with the discovery of new drugs, which starts with approximately 10,000 potential candidates of which 9,999 will be ruled out until the best of these compounds is selected. The chosen candidate will have a suitable equilibrium between efficacy and safety. The discovery phase can also be broken down in four stages:

      The pre-phase of research about the disease on which the future drug will act.

      Identifying a target disease where onto the drug can bind (known as biological or therapeutic target).

      Screening of the chemical compounds that perform on these targets.

      Optimization of these compounds until they produce the lead candidate.
Drug development stages


PREDISCOVERY OF TARGETS

As you could see from my previous post in this section, drug development is a really long process with high costs both in terms of human effort and financial investment. You can imagine then that before beginning this process we need to answer a set of questions to give us a clear idea about the next steps to take:

      What are the unmet medical needs today, what drug can be developed that allows us to establish a solution to a certain disease whose treatment or cure does not exist or is deficient currently.

      To have a broad knowledge about the illness which the drug will work on. This knowledge includes the causes of the disease, which is not always trivial.

      What proteins and genes are altered by the disease and how that affects the way in which these genes encode proteins.

      How cells and tissues are also modified.

      Finally, how the disease affects the whole patient.

Hence, this is a study from the smallest target where the disease can act (proteins and genes) to the largest (the patient).

Sources:  UTAustinX: UT.4.01x Take Your Medicine - The Impact of Drug Development.
               UC San Diego: Drug Discovery, Development & Commercialization.


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