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Drug Discovery

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Aala Santhosh Reddy, Aala Santhosh Reddy Editor Pharma Focus Asia

A large fraction of the drugs currently approved are derived from natural products which have always been a great source for new lead compounds offering new structural diversity Ulrich Betz Head of Strategic Innovation and Research Portfolio Management Merck KGaA

After more than a decade of showing disinterest, the pharma industry is taking a relook at natural products-based drug discovery. Pharma companies had shifted their focus from natural products to combinatorial chemistry because of lower costs, clarity on intellectual property and, importantly, because it could supply huge synthetic libraries in short periods. On the other hand, natural products were unable to generate enough numbers due to the slow and inefficient identification, isolation and purification technologies which couldn't keep pace with the High Throughput Screening methodologies. Apart from this, historically, deriving chemical entities from natural products was perceived to be difficult. This led the pharma companies to focus on combinatorial chemistry to deliver potential compounds to be used as drug leads. While combinatorial chemistry did just that, far too many compounds differed little in their properties, which affected drug discovery adversely.

As it happens, pharma companies today are under immense pressure owing to factors such as shrinking product pipelines, patent expiries of blockbusters and shorter drug discovery timelines, to name a few. Adding to these, increasing R&D costs and combinatorial chemistry's failure to deliver diverse and potent chemical entities have made pharma companies look at other alternatives.

Equipped with sophisticated technologies, the companies are now looking at mother nature for drug discovery. Researchers believe that natural products are the ideal sources for drug discovery as they possess drug-like properties and complement the "drug space" with their rich pool of unique molecular frameworks, both of which are highly desirable. Nature's pool offers a much higher, though complex, chemical diversity than combinatorial chemistry.

Natural products-based drug discovery is gaining prominence once again.

Advances in separation technologies are now helping pharma companies overcome the practical difficulties in using natural products in drug discovery. For instance, a combination of techniques such as High Pressure Liquid Chromatography with Ultraviolet Spectroscopy, Mass Spectroscopy and Nuclear Magnetic Resonance are increasingly being used in identifying suitable drug leads. Further, only a fraction of the around 300,000 plants identified have been systematically investigated for drug leads. This provides tremendous scope for identifying more leads from the huge library of nature, which is still unexplored. Also with the availability of advanced tools, the hurdles in using natural products in drug discovery are increasingly being overcome.

Today, a number of smaller pharma companies rely on natural products for generating drug leads and many global pharma companies, which had disowned or sold off their natural products divisions, are looking at outsourcing natural products-based drug discovery. While combinatorial chemistry and natural products have not tasted much success on their own, a combination of the two along with the advances in technology and chemical synthesis can show the way ahead for this industry.

Author Bio

Aala Santhosh Reddy