Journal of Exclusive Management Science – June 2018 - Vol 7 Issue 06 – ISSN 2277-5684

Drug Discovery and Development

Dr.K. S. Manjunatha
Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur-577548,
Karnataka, India.
Abstract
Drug discovery and development is a complex, high risk, time consuming and potentially highly
rewarding process. Pharmaceutical companies are spending millions of dollar per drug to bring it to the
market. The development of a new drug requires a technological expertise, human resources and huge
capital investment. It also requires strict adherence to regulations on testing and manufacturing
standards before a new drug comes into market and can be used in the general population, in fact,
some time it fails to come into market. All these factors just increase the cost for a new chemical entity
research and development. Bioinformatics in drug designing process made positive effect on
overall process and can accelerate various steps of drug designing, and reduce the cost and
over all time. Current note focuses on the role of bioinformatics in drug discovery and development
process.
Keywords: Bioinformatics; Drug; New chemical entity
Introduction
Drug discovery is the step-by-step process by which new candidate drugs are discovered.
Traditionally, pharmaceutical companies follow well-established pharmacology and chemistry-based
drug discovery approaches, and face various difficulties in finding new drugs [1]. In the highly
competitive ‘‘winner takes all’’ pharmaceutical industry, the first company to patent a new
chemical entity (NCE i.e., new drug candidate) for a specific treatment takes all the spoils,
leaving other competitors to mostly wait for patent expirations to partake in the
largesse [1]. Nowadays, therefore, Pharmaceutical companies invest heavily in all those
approaches that show potential to accelerate any phase of the drug development process [2].
The increasing pressure to generate more and more drugs in a short period of time with low
risk has resulted in remarkable interest in bioinformatics [3]. In fact, now there is an existence of
new, separate field, known as computer- aided drug design (CADD) [4].
Drug Target Identification
One of the major thrusts of current bioinformatics approaches is the prediction and
identification of biologically active candidates [2], and mining and storage of related information (Table
1). Drugs are usually only developed when the particular drug target for those drugs’ actions
have been identified and studied. The number of potential targets for drug discovery process is
increasing exponentially. Mining and warehousing of the human genome sequence using
bioinformatics has helped to define and classify the nucleotide compositions of those genes, which are
Responsible for the coding of target proteins, in addition to identifying new targets.

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S. No Database Information
1 Drug bank Wishart, et al.[9] The Drug Bank database is a blended bioinformatics and chemo
informatics resource that combines detailed drug (i.e., chemical,
pharmacological and pharmaceutical) data with comprehensive
drug target(i.e., sequence, structure, and pathway) information
2 Therapeutic target DB Zhu, The therapeutic target database (TTD) is a drug database
et al. [10] designed to provide information about the known therapeutic
protein and nucleic acid targets described in the literature, the
targeted disease conditions, the pathway information and the
corresponding drugs/ligands directed at each of these targets
3 STITCH Kuhn, et al. [11] STITCH (‘search tool for interactions of chemicals’) is a
searchable database that integrates information about
interactions from metabolic pathways, crystal structures,
binding experiments and drug-target relationships. Text mining
and chemical structure similarity is used to predict relations
between chemicals. Each proposed interaction can be traced
back to the original data sources
4 Super Target Hecker, et al. Super Target is a database that contains a core dataset of about
[12] 7,300 drug-target relations of which 4,900interactions have been
subjected to a more extensive manual annotation effort. Super
Target provides tools for 2D drug screening and sequence
comparison of the targets

Table 1: Drug Target Database.

Drug Target Validation
Bioinformatics also provides strategies and algorithm to predict new drug targets and to store
and manage available drug target information. After the discovery of ‘‘potential’’ drug targets, there is
an inappreciable need to establish a strong association between a putative target and disease of
interest [7]. The establishment of such a key association provides justification for the drug
development process. This process, known as target validation, is an area where bioinformatics
is playing a significant role (Figure 1). Drug target validation helps to moderate the potential for failure
in the clinical testing and approval phases [2].
Cost Reduction
The current high cost of drug discovery and development is a major cause for
concern among pharmaceutical companies [13]. Along with increasing productivity, pharmaceutical
companies also aim to reduce the high failure rate in the drug discovery process so that increased
number of drugs able to hit the market [14]. The high cost of various phases of clinical trials acts as
limiting factors for number of drugs, which can be developed by pharmaceutical companies, and
hence selecting the compounds with the best chances for approval is critical [15]. The costs of
drug discovery and development generally include total costs from discovery to approval though some
studies have included the costs of failed drugs and the costs for commercialization [13, 16].
There is also a cost associated with the elongated process, beginning from discovery all the way to
final approval [15,17]. Advances in bioinformatics accelerate drug discovery process, beginning
with drug target identification and validation (viz., Docking), to assay development, and
virtual-high-throughput screening (v- HTS)-all with the goal of identifying new potential
chemical entities. Bioinformatics provides more efficient target discovery and validation
approaches, thus help to ensure that more drug candidates are successful during the approval
Process and making it cost-effective[3].

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 Journal of Exclusive Management Science – June 2018 - Vol 7 Issue 06 – ISSN 2277-5684

Figure 1: The role of bioinformatics in different stages of drug discovery process.

Promote Novel Drug Development
There are some collateral costs that bother the pharmaceutical industry [18]. These
costs include commercialization costs, litigation and drug-recall costs, and general costs to society
[17, 19, and 20]. Commercialization costs for new drug to be about $250 million per approved drugs,
are high mainly because most ‘‘new’’ drugs approved are essentially functional replicas of drugs that
already exist [16, 21]. Most of the copycat drugs are being commercialized to handle the illness for
which there are drugs already; thus, there is a need of interface that can attract the attention of
both physicians and patients who already have access to similar medication [22].
Bioinformatics can act as proper interface, and provides new approaches and
opportunities to pharmaceutical companies to efficiently discover potential drug targets and
develop novel drugs [2]. If drugs are not commercialized in competition with already existing
equivalents, their commercialization costs are expected to fall significantly [23].
Barriers to Bioinformatics Progress in Drug
Design Process
Bioinformatics efforts did not make any impeccable changes in the drug discovery and development
process. This may be because the practice of bioinformatics is relatively new and has only
attained prominence in the years following the partial completion of the Human Genome
Project [24]. Till now, bioinformatics has not made any considerable impact, as projected earlier, on
the cost of drugs. The pharmaceutical industry continues to witness rising costs and withdrawals
of drugs from the market after they had been approved and commercialized-
because of multiple documented cases of adverse drug reactions [25]. It has been observed that
several pharmaceutical industries are facing drug discovery and development related
challenges. These challenges range from high cost of drug discovery to the lengthy and risky trials
and approval process, and some time, withdrawal of previously approved drugs from the market
and the innovation gap resulting from the dogged quest for blockbuster drugs [1,12,13]. Bioinformatics
was widely projected to strengthen the identification of drug targets [6]. The fact that these problems
remain mostly unsolved, despite significant bioinformatics investments, is an indication of a larger
problem [26,27].

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Conclusion
Drug designing is a very complex, expensive and time consuming process. Bioinformatics provide
a huge support to overcome the cost and time context in various ways. Bioinformatics provides wide
range of drug-related databases and software, which can be used for various purposes, related to
drug designing and development process. Bioinformatics is still in their developmental
phase and presently facing some hurdles, they show enough potential to help drug
developments.
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