Drug discovery and design is one of those areas which can be almost categorized as rocket science. The sheer complexity of human cellular physiology with its convoluted mechanism of actions coupled with multiple dimensions of variables makes drug discovery a truly challenging task. Dimensions like patient population sub-types, age, genetic variations, dietary patterns, gender, life style and many such factors all contribute to determining the drug efficacy and toxicity making the process really challenging. At a broad level a drug is evaluated based on two metrics Efficacy and Toxicity.
Efficacy of a drug is defined in terms of cure or elimination of disease condition and/or only mitigation of disease associated conditions. Toxicity or side-effects is defined as unintended and unwanted impact of the drug which causes or triggers other disease conditions. It is a well known pharmacology fact that every drug will show side-effects beyond certain dosages. Or rather every drug can be a poison at certain dosage. The objective of drug design is to come up with a molecule which shows the maximum targeted efficacy with acceptable side-effects.
For drug design and discovery, a cell view can be simplistically thought of as a huge network of proteins which are linked by different mechanisms which form the nuts and bolts of the biochemical structure of the cell. These cells put together form different organ tissues. The organs put together constitute the human body. For designing a drug the designer needs to identify first which biological target (type of protein) and it combinations to target in the specific cell type. Then the next stage is to come up with drug molecule which can be administered and which will bind to the target protein to achieve desired effect.
Hence the drug discovery process starts with a Biology focus and transitions to Chemistry focus with tight iterative loop between the two. The bad and ugly side of the drug can be due to biology or chemistry reasons. The biology angle is consequence of the biological target chosen for manipulation by a drug for specific clinical endpoint response. The chemistry angle is possibly due to drug binding and manipulating other unintended biological targets in addition to the desired ones during the Absorption, Distribution, Metabolism and Excretion (ADME) process.
With the emphasis or move towards personalized medicine the implicit move is from a broad target-based binding of drug to specificity of biological target binding. Hence in any drug discovery process getting both the biology and chemistry right is important and required. Also in this context if the Biology is not optimal or correct no amount of good chemistry can possibly correct it. When a drug displays its bad and ugly side the question is whether it is due to Biology or Chemistry. Knowing this is extremely important as enables proper channeling of research focus as a follow-on process.