BioLeap and GSK have entered into an agreement whereby BioLeap will design novel
lead compounds for "difficult" drug targets. The targets (not disclosed) are
ones for which conventional approaches, like high throughput screening, have
failed to yield a viable chemical starting point. Typically these are in areas
of high unmet medical need.
BioLeap will use its computational fragment-based drug design platform to
conceive compounds de novo that are molecularly tailored to bind to the target.
GSK will synthesize and test the compounds in biochemical and cellular assays.
The process will iterate until GSK selects a Lead Candidate. The terms of the
agreement for services were not disclosed.
David Pompliano, PhD, CEO of BioLeap said, "We are very pleased to be working
with GSK to accelerate the discovery of truly novel medicines. BioLeap`s
platform reliably predicts the effect of compound modifications on target
affinity, thus minimizing unproductive guesswork during drug discovery, and
producing a better drug candidate more quickly."
About BioLeap
BioLeap is a leader in computational fragment-based drug design. The company`s
proprietary design technology and process successfully addresses one of the
biggest problems in pre-clinical drug discovery: the limitation of drug like and
patentable leads for important biological targets. BioLeap is using its
completely "in-silico" platform to quickly and accurately predict
fragment-protein binding information that provides drug designers new insights
that enable them to efficiently create new and improved drug molecule
candidates. The BioLeap computational approach addresses the time, cost, and low
probability of success limitations imposed by traditional library screening and
lead optimization methods. BioLeap is utilizing its capabilities to advance its
own internal preclinical stage programs while collaboratively enabling
non-competing programs with numerous pharmaceutical partners.
A multi-institutional team of Boston-area researchers has discovered a chemical that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.
These cells, known as cancer stem cells, are thought to enable cancers to spread — and to reemerge after seemingly successful treatment. Although further work is needed to determine whether this specific chemical holds therapeutic promise for humans, the study shows that it is possible to find chemicals that selectively kill cancer stem cells. The scientists’ findings appear in the August 13 advance online issue of Cell.
“Evidence is accumulating rapidly that cancer stem cells are responsible for the aggressive powers of many tumors,” says Robert Weinberg, a Member of Whitehead Institute for BiomedicalResearch and one of the authors of the study. “The ability to generate such cells in the laboratory, together with the powerful techniques available at the Broad Institute, made it possible to identify this chemical. There surely will be dozens of others with similar properties found over the next several years.”
“Many therapies kill the bulk of a tumor only to see it regrow,” says Eric Lander, Director of the Broad Institute of MIT and Harvard, and an author of the Cell paper. “This raises the prospect of new kinds of anti-cancer therapies.”
An emerging idea in cancer biology is that tumors (breast, prostate, colon, lung, etc.) harbor a group of cells with the unique ability to regenerate cancers. In addition to promoting tumor growth, these so-called cancer stem cells are largely resistant to current cancer therapies. If it were possible to identify chemicals that selectively kill cancer stem cells, such chemicals might become critical candidates for future drug development.
However, researchers have struggled to study cancer stem cells directly in the laboratory. The cells’ relative scarcity compared to other tumor cells, combined with a tendency to lose their stem cell-like properties when grown outside of the body, have severely limited the amount of material available for analysis.
To overcome these hurdles, Broad and Whitehead Institute researchers drew upon recent findings from Weinberg and his colleagues that suggested a way to generate in the laboratory large numbers of cancer cells with stem cell-like qualities. The technique works by coaxing adult cells to undergo a critical change (known as an “epithelial-to-mesenchymal transition”) that alters their shape and motility. At the same time, the cells also adopt similar properties as stem cells.
“A critical aspect of our work was to generate relatively homogenous and stable populations of cancer stem-like cells that could then be used for screening,” says Tamer Onder, a former graduate student in Weinberg’s lab and co-first author of the study. (Onder is now a postdoctoral research fellow at Children’s Hospital in Boston.) “We were able to achieve this by inducing the cancer cells into an epithelial-to-mesenchymal transition using novel reagents that we had developed in the lab.”
With an ample number of stem cells in hand, the Broad-Whitehead team undertook a large-scale analysis of thousands of chemical compounds, applying automated methods to search for ones with activity against breast cancer stem cells. From a pool of more than 30 promising candidates, the researchers identified a compound with surprising potency.
The compound, called salinomycin, kills not only laboratory-created cancer stem cells, but also naturally occurring ones. Compared to a common chemotherapeutic drug prescribed for breast cancer (known as paclitaxel), salinomycin reduced the number of cancer stem cells by more than 100-fold. It also diminished breast tumor growth in mice.
To further dissect the function of salinomycin, the researchers also examined its genetic effects. Previous studies of tumors from breast cancer patients have revealed groups of genes that are highly active in cancer stem cells. Many of these same genes are linked with particularly aggressive tumors and poor patient prognoses. The researchers’ studies show that salinomycin (but not paclitaxel) treatment can decrease the activity of these genes, revealing a possible molecular basis for the chemical’s biological effects.
“Our work reveals the biological effects of targeting cancer stem cells,” says co-first author Piyush Gupta, a researcher at the Broad Institute. “Moreover, it suggests a general approach to finding novel anti-cancer therapies that can be applied to any solid tumor maintained by cancer stem cells.”
Although the new findings signal a noteworthy scientific milestone, it is still too early to know whether cancer patients will reap benefits from it. Additional research is needed to determine exactly how salinomycin works to kill cancer stem cells and if it can wield the same tumor-reducing power in humans as it does in mice. These types of analyses generally take several years to complete.
But even with such tempered enthusiasm, there is also cause for optimism. In the current study, just 16,000 chemical compounds were tested, of which a small subset showed toxicity against cancer stem cells. Therefore, deeper investigations of these compounds as well additional tests of broader collections of chemicals may yield other potential additions to the anti-cancer arsenal.
7 Sep 2009 , Monheim : Bayer CropScience has invested EUR 4.9 million in the expansion of the compound logistics at its Monheim site. It has one of the most modern facilities in the world for storing chemical compounds. The company’s scientists use the 2.2 million or so substances currently in the collection to search for promising active ingredients for innovative crop protection products. After just 15 months of construction, the extension was inaugurated at a ceremony attended by Dr. Alexander Klausener, Head of Research at Bayer CropScience.
The purpose of the compound logistics is to store, prepare and distribute substances prior to comprehensive biological testing. “We are now in a position to pursue our research and development activities even more efficiently than before,” Dr. Klausener explained. With expenditures of EUR 649 million in research and development (2008), Bayer CropScience is one of the leading companies in its sector.
The central feature of the compound logistics, which has been extended to cover more than 1,000 square meters, is the substance storage area. The automatic miniload warehouse with some 24,000 storage positions now has space for about 7.6 million vials containing minute quantities of different chemical compounds. Placed side by side, the vials would cover a distance of around 161 kilometers. A total of 16 robots and retrieval units “work” in the facility, where they achieve a high throughput. They quickly supply researchers in Bayer CropScience’s institutes with the exact quantities they need; this spares resources and, above all, ensures “just in time” delivery. The investigational substances undergo a comprehensive screening procedure, in which they are tested to see whether they have a desired effect, for example in controlling fungal pathogens, insect pests or weeds, and could thus be suitable as the starting point for developing a new product.
About Bayer CropScience
Bayer is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer CropScience AG, a subsidiary of Bayer AG with annual sales of about EUR 6.4 billion (2008), is one of the world’s leading innovative crop science companies in the areas of crop protection, non-agricultural pest control, seeds and plant biotechnology. The company offers an outstanding range of products and extensive service backup for modern, sustainable agriculture and for non-agricultural applications. Bayer CropScience has a global workforce of more than 18,000 and is represented in more than 120 countries. This and further news is available at: www.press.bayercropscience.com.
The guilt-free double Whopper experience is inching closer.
A small molecule that turns off the genes responsible for making fat cells has been discovered by a team of Baylor College of Medicine and Japanese researchers.
Dubbed “fatostatin,” the molecule blocks a protein in the cell that starts the cascade of events that turns on the 63 genes in the nucleus responsible for the generation of fat cells, said Salih Wakil, professor of biochemistry and molecular biology at BCM.
The report appears in the journal Chemistry and Biology.
“That is the exciting thing,” said Wakil. “This goes to the most basic level of the expression of genes that cause fat.”
When mice with a predisposition to be obese received fatostatin, they lost weight, their cholesterol and fatty acid synthesis decreased. They had less resistance of insulin (a factor in diabetes), and their livers, which were pale because of fat buildup, returned to normal.
Drugs that lower cholesterol already exist, but they block only a single enzyme in the fat-generating pathway. Fatostatin stops the process at the beginning, said Wakil.
Wakil said one of his colleagues, Motonari Uesugi, now of Kyoto University in Japan, discovered the compound by screening a library of an estimated 10,000 compounds.
Lutfi Abu-Elheiga, associate professor of biochemistry and molecular biology at BCM was also a major contributor.
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