Featured Research

from universities, journals, and other organizations

Molecular Architects Create New Cancer Preventives

August 23, 2000
Johns Hopkins University
Researchers at Johns Hopkins have developed a modified form of vitamin D and determined that it helps delay the onset and reduce the number of skin cancers in lab mice. Unlike vitamin D, though, the new compound does not cause calcium to seep from the bones.


Researchers at The Johns Hopkins University have developed a modified form of vitamin D and determined that it helps delay the onset and reduce the number of skin cancers in lab mice. Unlike vitamin D, though, the new compound does not cause calcium to seep from the bones.

If not for the calcium loss problem, large doses of vitamin D could be used to reduce the odds of developing cancer in patients whose medical history, genetic heritage, or environmental exposures put them at increased risk. Depending on the results of further tests in animals and potential tests in humans, the new compound and others to follow it may provide an important alternative approach to reducing cancer risk for such patients.

Gary Posner, Scowe Professor of Chemistry in Johns Hopkins' Krieger School of Arts and Sciences and one of the new compound's creators, will describe work to design and test the compounds at a meeting of the American Chemical Society in Washington, D.C., this week.

In the July/August issue of "Carcinogenesis," Posner and Thomas Kensler, professor at the Johns Hopkins School of Public Health, published results of tests in mice of four modified forms of vitamin D, called deltanoids or vitamin D analogs. The deltanoids were applied to the skin of mice also treated with a carcinogen.

All four deltanoids diminished the number of skin tumors without any significant effects on calcium loss or weight gain, which is usually adversely affected by vitamin D. The most effective preventive compound was a doubly modified "hybrid" compound that contained fluorine.

The new deltanoids are, for the most part, identical to vitamin D, which is normally generated in the skin during exposure to sunlight. In several areas, though, Posner and his students have given the compounds' molecular structures several small "tweaks."

"We call our work molecular architecture, because at the submicroscopic level we are altering the structures of known compounds or designing new compounds from scratch," explains Posner.

Those alterations can include adding components to, taking things away from, and re-orienting parts of the molecule.

"It's still a science and an art combined," Posner explains. "It's not yet possible for anyone to go from a new chemical structure and to predict in advance the biological properties of that new structure."

This inability of molecular architects to predict exactly the results of their design changes can sometimes force them to rely on their intuitive sense of which change will produce the desired result. But the design process is also rational, Posner emphasizes, because it is based to the greatest extent possible on principles established through prior experimentation. Earlier research in the deltanoids included many efforts by pharmaceutical companies to improve vitamin D.

"What we did was to take some of the best structural changes that large pharmaceutical companies have made public," Posner says, "and incorporated those changes with a structural change that we discovered here 10 years ago in a different portion of the molecule."

Posner's group found that if they added a methylene group, composed of one extra carbon atom and two hydrogen atoms, to an area of the vitamin D molecule known as the A ring, the molecule caused much less calcium loss.

Based on the research of another lab, Posner's group also added two fluorine atoms to the molecule at an ideal point to reduce the body's ability to break down and metabolize the vitamin D analogs. This not only reduces the levels of potentially harmful metabolites produced by the analogs, it also keeps the analogs active in the body longer.

The changes are all small compared to the size of the vitamin D molecule, which has a total of 27 carbon atoms. But they make a significant difference in its effects.

"You might think you'd have to change large portions of the molecule to change its biological effects, but it's well-known that you can do that by changing small portions of the molecule," Posner says.

Further animal tests of the analog on different types of tumors are planned in Kensler's lab. If the new tests and tests in humans prove successful, doctors might one day be able to consider treating patients at high risk for cancer with the compound, probably applying it as a topical gel.

Meanwhile, Posner's lab is already at work on yet another generation of improved deltanoids.

"There's a lot of trial and error," he says. "My research group has, over the years, made about 100 different vitamin D analogs. And the winners are probably limited to 10. If you consider the more general issue in the pharmaceutical industry, though, going from the bench to a drug, typically it's one in many thousands of compounds. And that gives you a feeling for just how far rational design can or can't come."

This research was funded in part by grants from The National Cancer Institute of the National Institutes of Health.


For recorded quotes from Posner, go to http://www.jhu.edu/news_info/news/home00/aug00/vitamind.html

Story Source:

The above story is based on materials provided by Johns Hopkins University. Note: Materials may be edited for content and length.

Cite This Page:

Johns Hopkins University. "Molecular Architects Create New Cancer Preventives." ScienceDaily. ScienceDaily, 23 August 2000. <www.sciencedaily.com/releases/2000/08/000817143445.htm>.
Johns Hopkins University. (2000, August 23). Molecular Architects Create New Cancer Preventives. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2000/08/000817143445.htm
Johns Hopkins University. "Molecular Architects Create New Cancer Preventives." ScienceDaily. www.sciencedaily.com/releases/2000/08/000817143445.htm (accessed July 31, 2014).

Share This

More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.


Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News


      Free Subscriptions

      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile

      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?

      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins