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By Dhaval Shah

Dhaval ShahI have always wondered how a drug molecule is invented and how it reaches the commercial market. Discovery of a drug molecule and its commercialization are the initial and final states of drug development respectively, and they may be the only stages visible to the general public. But behind the scenes the story of drug discovery and development is much more complex.

In fact, a potential drug molecule must be evaluated by various departments such as pharmacology, pharmacokinetics (PK), pharmaceutical development, and safety in order to undergo the very critical analysis of assessing whether the compound is worth pursuing for further development. In my experience, however, many graduate students are not very familiar with how all these departments function and interact in the industry in order to select the most beneficial and successful candidates in regards to therapeutic efficacy, safety, drug delivery, and patient compliance.

It is clear to me that the most important step in the whole process is the selection of a candidate. As graduate students, we ask the following questions of ourselves: How is a drug candidate selected for development? What are the properties needed to be considered for this selection process? What studies are needed to determine the required properties for selection of a drug candidate?

To my knowledge, ADME (absorption, distribution, metabolism, and excretion) properties, SAR (structure, activity, and relationship), and physicochemical properties can change due to presence of various functional groups such as H-bond donors and acceptors. This affects cellular permeability, PK parameters, (i.e., Cmax, AUC, t1/2), and safety assessments. These parameters in turn determine the boundaries of the therapeutic window for a compound and the potential for adverse effects. Therefore a number of studies must be assessed before a candidate is selected for continued development. A candidate is selected by putting all these pieces together. Certainly all of these studies are time consuming, but they play very important roles in avoiding pitfalls and reducing the drop-out ratio from the drug pipelines.

I am currently an active member of the AAPS Drug Candidate Selection (DCS) focus group. The group deals with the developability assessment of a drug candidate by using various disciplines to narrow down the selection in order to minimize the risk and maximize the chances of selecting a successful drug candidate. The group provides me with useful information about the involvement of different scientific areas as well as the complexity of the drug candidate selection process through effective communication and knowledge sharing.

Dhaval Shah is a Ph.D. candidate in pharmaceutical science and drug design at the Arnold & Marie Schwartz College of Pharmacy, Long Island University.