The future of drugs is all in the family

In a first-ever comprehensive study of the species origins of nature-derived drugs, it is shown that drug-producing species are concentrated and clustered in a limited number of families, refuting the conventional view that as every nature species produces biologically active molecules, one can find drugs from almost any major block of species groups if one looks for them hard enough.

Whether you have a mild headache or you are running a fever, there is a high chance that the that is used to treat you comes from nature. Today, about half of the drugs on the market were discovered by screening collections of small molecules made by bacteria, fungi, snails, leeches and other such species.

In Singapore, the top selling drugs for treating common ailments that are derived from nature include No. 12 Aspirin (for pain, fever and inflammation), No. 2 Amoxil (antibiotic), No. 7 Procodin (for cough), No. 8 Beserol (muscle relaxant) and No. 3 Ventolin (for asthma and ).

Worldwide, eight of the top 20 selling drugs available today are derived from nature, some of which include No. 2 and No. 9 Crestor (both for treating cholesterol), No. 4 Advair Diskus (for asthma), No. 15 Lantus (for diabetes), and No. 18 Diovan (for hypertension).

Another six of the top 20 selling drugs in the world are mimics of natural products. No. 6 Abilify (for psychosis and depression), No. 7 Singulair (for asthma), No. 10 Cymbalta (for depression and ) are some of the examples.

Although the pharmaceutical industry has made serious efforts to get away from relying on the natural world by attempting to create rationally designed drugs using synthetic compounds, nature-derived drugs still constitute a substantial percentage (26%) of recently approved drugs.

Nature-derived drugs not in every species

The conventional view about nature-derived drugs is that as every nature species produces biologically active molecules, one can find drugs from almost any major block of species groups if one looks and searches for them hard enough.

This view has been proven wrong in a first-ever comprehensive study of the species origins of nature-derive drugs conducted by researchers from the National University of Singapore (NUS) and Tsinghua University. Published in Proceedings of the National Academy of Sciences of the United States of America in July 2011, the research showed that drug producing species are concentrated and clustered in a limited number of families.

Data analysed by the research team showed that out of 886 nature-derived drugs discovered in the last 50 years (1961 to 2010), 88% or 783 were from previously known drug producing families. A further 41 were from near neighbours of known productive families. Only 62 came from 'dark horses' that were completely outside of the known clusters.

Lead researcher Professor Chen Yu Zong from the Department of Pharmacy at NUS, said, "In each kingdom of life, the drug-producing families are strongly clustered. Only a limited number of molecular scaffolds are privileged drug-like structure made by specific metabolic genes in certain species families. Some families with lots of bioactive compounds have never produced a drug because their metabolic genes are not capable of producing privileged drug-like structures, even though they can produce bioactive structures. "

Focus on family members

The findings from this research can now point us to the direction on where to concentrate on the search for new drugs, and that is from pre-existing drug-productive families.

In explaining this rationale, Prof Chen said, "We have identified and highlighted a number of families that have not produced an approved drug but are likely in the drug-producing clusters and potentially produce future approved drugs. Just like by knowing the clustered distribution patterns of oil fields, one knows where to place their bets on the next oil field based on existing findings. For instance, if one finds the first oil-producing well somewhere in the South China seas, by knowing that oil fields tend to be clustered, there is a higher chance in finding the next oil fields by a search of the surrounding areas."

By focusing on pre-existing drug-productive families, resources can be concentrated on manipulating and expanding the families for producing new, as well as existing drugs. In addition, these pre-existing drug-productive families can be studied on why they produce privileged drug-like structures, and the knowledge can be used for designing new and novel drugs.

The potential impact of the research, concludes Prof Chen, is "to promote bioprospecting efforts on those species and species families that are likely to produce new drugs, thus enabling the increase of new drug productivity."

Provided by National University of Singapore

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

New 'matrix of harm' for drugs of abuse

Mar 23, 2007

A new study published today in the Lancet proposes that drugs should be classified by the amount of harm that they do, rather than the sharp A, B, and C divisions in the UK Misuse of Drugs Act.

New Way To Predict Drug Side Effects

Nov 11, 2009

Predicting the side-effects of a drug is not simple task. The human body has more than 1,500 molecules that are known to be involved in various diseases, and often a drug designed to hit one of these targets will also hit ...

Scientists solve mystery of polyketide drug formation

Apr 01, 2008

Many top-selling drugs used to treat cancer and lower cholesterol are made from organic compounds called polyketides, which are found in nature but historically difficult for chemists to alter and reproduce in large quantities.

Toward an effective treatment for a major hereditary disease

Oct 13, 2008

Scientists are reporting a key advance toward developing the first effective drug treatment for spinal muscular atrophy (SMA), a genetic disease that involves motor neuron loss and occurs in 1 out of every 6,000 births. SMA ...

Recommended for you

WHO: Millions of Ebola vaccine doses ready in 2015

17 hours ago

The World Health Organization says millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines will start being tested in March.

Added benefit of vedolizumab is not proven

Oct 23, 2014

Vedolizumab (trade name Entyvio) has been approved since May 2014 for patients with moderately to severely active Crohn disease or ulcerative colitis. In an early benefit assessment pursuant to the Act on the Reform of the ...

Seaweed menace may yield new medicines

Oct 22, 2014

An invasive seaweed clogging up British coasts could be a blessing in disguise. University of Greenwich scientists have won a cash award to turn it into valuable compounds which can lead to new, life-saving drugs.

User comments