1 Million Billion Billion Billion Billion Billion Billion: Number of Undiscovered Drugs

A new voyage into "chemical space" -- occupied not by stars and planets but substances that could become useful in everyday life -- has concluded that scientists have synthesized barely one tenth of 1 percent of the potential medicines that could be made. The report, in the journal ACS Chemical Neuroscience, estimates that the actual number of these so-called "small molecules" could be 1 novemdecillion (that's 1 with 60 zeroes), 1 million billion billion billion billion billion billion, which is more than some estimates of the number of stars in the universe.

A new voyage into "chemical space" -- occupied not by stars and planets but substances that could become useful in everyday life -- has concluded that scientists have synthesized barely one tenth of 1 percent of the potential medicines that could be made [Credit: Web]

Jean-Louis Reymond and Mahendra Awale explain that small molecules, which are able to cross cell walls and interact with biological molecules in the body, are prime targets for scientists who develop new medicines. Most existing medications are small molecules. The authors focused on the "chemical space" inhabited by all of the small molecules that could possibly exist according to the laws of physics and chemistry. 

Researchers have identified millions of these compounds -- the ACS' Chemical Abstracts Service database contains almost 67 million substances. Reymond and Awale estimate that the molecules synthesized and tested as potential drugs so far represent less than 0.1 percent of chemical space. To aid researchers looking for new ways to prevent and treat disease, they set out to find the best ways to search for new small molecules.

The authors discuss several ways of getting a handle on chemical space, including by the size, shape and makeup of molecules. They show how computers can help researchers efficiently narrow a search for a new drug candidate. Computer modeling of chemical interactions can help researchers find a handful of promising molecules to synthesize and test in the lab. "Small molecule drugs are essential to the success of modern medicine," the authors note, and suggest that their methods may be particularly useful for finding new pharmaceuticals that target the central nervous system.

Source: American Chemical Society [June 06, 2012]

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Moderate marijuana use doesn’t damage lung function

Occasional and low cumulative marijuana use is not associated with adverse effects on pulmonary function, a new study has found. 

Exposure to tobacco smoke causes lung damage with clinical consequences that include respiratory symptoms, chronic obstructive pulmonary disease, and lung cancer. 

Mark J. Pletcher and his colleagues from the University of California examined associations between marijuana, both current and lifetime exposure, and pulmonary function. 

The Coronary Artery Risk Development in Young Adults (CARDIA) study is a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 1985-August 2006) in a group of 5,115 men and women in 4 U. S. cities. 

Lifetime exposure to marijuana joints was expressed in joint-years, with 1 joint-year of exposure equivalent to smoking 365 joints or filled pipe bowls. Lung function was assessed by the measurements of forced expiratory volume in the first second of expiration (FEV1) and forced vital capacity (FVC), with lower measures corresponding to poorer lung function. 

More than half of participants reported current marijuana smoking, tobacco smoking, or both at 1 or more examinations. The median intensity of tobacco use in tobacco smokers was substantially higher - 8-9 cigarettes per day, than the median intensity of marijuana use in marijuana smokers -2-3 episodes in the last 30 days. 

In fully adjusted models that considered 4-level categorizations of current and lifetime exposure to tobacco and marijuana, tobacco smoking was associated with a lower FEV1 and current smoking with a lower FVC. 

In contrast, exposure to marijuana was associated with higher FVC and lifetime exposure with higher FEV1. At low lifetime exposure levels, increasing marijuana use was associated with an increase in both FEV1 and FVC. 

"With up to 7 joint-years of life-time exposure e. g., 1 joint a day for 7 years or 1 joint/week for 49 years, we found no evidence that increasing exposure to marijuana adversely affects pulmonary function," the researchers said. 

At more than 10 joint-years of lifetime exposure, there was a nonsignificant decline in FEV1, but there was a significant decline in FEV1 at more than 20 episodes of marijuana use per month. 

"Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function," they said. 

"It is more difficult to estimate the potential effects of regular heavy use, because this pattern of use is relatively rare in our study sample; however, our findings do suggest an accelerated decline in pulmonary function with heavy use and a resulting need for caution and moderation when marijuana use is considered," the researchers added. 

The study has been recently published in JAMA. 

Source: Top News [January 11, 2012]

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Work sheds new light on medicinal benefits of plants

Scientists from institutions around the nation and the world have collaborated to develop new resources poised to unlock yet another door in the hidden garden of medicinally important compounds found in plants. 

Periwinkle (Catharanthus roseus) is a source of potent chemotherapeutic drugs and a common horticultural plant found around the world [Credit: David K. Liscombe]

The resources were developed by the Medicinal Plant Consortium (MPC) led by Joe Chappell, professor of plant biochemistry at the University of Kentucky, Dean DellaPenna, professor of biochemistry at Michigan State University and Sarah O'Connor, professor of chemistry at Massachusetts Institute of Technology and now at the John Innes Centre in Norwich, England. They grew out of a $6 million initiative from the National Institutes of Health (NIH) to study how plants produce the rich diversity of chemical compounds, some of which are medicinally important. 

"Our major goal in this project has been to capture the genetic blueprints of medicinal plants for the advancement of drug discovery and development," said Chappell, project coordinator for the MPC. 

"Most people are familiar with the natural products we derive from plants," Chappell added. "These include the delightful fragrances that go into perfumes, soaps, household cleaning products and more. Just as the sensory properties of plants interact with and trigger your sense of smell, plants' natural compounds can target and cause a reaction within your body. This gives them tremendous pharmaceutical potential." 

The MPC project includes participants from Michigan State, Iowa State University, the University of Mississippi, Purdue University, Texas A&M University, MIT, and the John Innes Centre, in addition to UK. The associated researchers represent a broad spectrum of expertise from plant biology and systematics to analytical chemistry, genetics and molecular biology, and drug development from natural products. 

DellaPenna, MPC co-project coordinator, said, "Thanks to the funding received for these projects, the talents and skills of experts from all of these institutions have been brought together with the goal of forging a new model in drug discovery." 

Some well-known medicines have come from plants. For instance, the foxglove plant gives us the cardiac muscle stimulant digoxin, and the periwinkle plant offers a source for the widely used chemotherapy drugs vincristine and vinblastine. These and many other medicinal plants, often commonly found in household gardens and flower boxes, represent cornucopias of compounds ripe for discovering and developing diverse medicinal applications. 

"The current understanding of the molecules and genes involved in the formation of plant-derived medicinal compounds is very incomplete. However, the ability to conduct genome-wide studies of model plant species has resulted in an explosive increase in our knowledge of and capacity to understand the biological processes," added O'Connor, also an MPC co-project coordinator. 

During this two-year project funded through the American Recovery and Reinvestment Act (ARRA), researchers from two consortia set out to develop a collection of data that would aid in understanding how plants make chemicals, a process called biosynthesis. This knowledge ultimately could make it possible to engineer plants to produce larger quantities of medicinally useful compounds as well as different versions with other therapeutic potential. 

To develop the resources, the researchers studied the genes and chemical composition of 14 plants known for their medicinal properties or compounds with biological activity. These included plants such as foxglove, ginseng, and periwinkle. Altogether, these efforts are now providing a rich toolbox for researchers to discover the means for how nature's chemical diversity is created, thus empowering efforts to uncover new drug candidates and increase the efficacy of existing ones. 

The work of the MPC included obtaining materials for all the medicinal plants used in this study. The MPC then determined the plants' chemical profiles and obtained their genetic blueprints to study how genes control the various chemical compositions. 

"This work offers a valuable data resource for understanding the genes, enzymes and complex processes responsible for the biosynthesis of important plant-derived drugs," said Warren Jones, who manages this and other research grants in biotechnology at NIH's National Institute of General Medical Sciences, through which the ARRA funds were provided. "The collaborative effort should greatly contribute to our ability to understand and exploit the rich biochemistry found in plants."

Source: University of Kentucky [December 15, 2011]

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