Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study finds new designer drug is potent treatment for chronic myelogenous leukemia

21.02.2005


More potent and highly selective therapy effective in treating Gleevec-resistant disease



A laboratory study led by researchers at Dana-Farber Cancer Institute has shown that a potent and highly selective therapy for chronic myelogenous leukemia (CML) may ultimately be more effective than Gleevec®, the current standard of care. The researchers report in the February issue of Cancer Cell that the new compound, AMN107, is about 20 times more potent than Gleevec and is effective in treating Gleevec-resistant disease in model systems. Discovered by and in development with Novartis Pharma AG, AMN107 is a small molecule tyrosine kinase inhibitor.

"While Gleevec represents a major treatment advance for CML – approximately 95 percent of patients treated with Gleevec achieve remission – there clearly is a need for therapies that produce longer remissions, are active against advanced disease, and can be used when Gleevec loses effectiveness," says Dana-Farber’s James Griffin, MD, senior author of the study.


Gleevec shuts down CML by blocking the function of Bcr-Abl, the abnormal tyrosine kinase protein in the leukemic cells that causes them to grow too quickly. However, it does not bind very tightly to this protein, and patients can develop a resistant type of Bcr-Abl that no longer binds to Gleevec at all.

Using rational drug design to circumvent these shortcomings, researchers at Novartis determined the crystal structure of Bcr-Abl, and then constructed compounds that would lock into the receptor more securely than Gleevec. Investigators at Dana-Farber tested the new compounds to measure their effectiveness against CML in laboratory cell cultures and mice with the disease.

Data from the study published in Cancer Cell showed that in experiments with laboratory samples of CML cells, AMN107 killed the cells more effectively than Gleevec. In follow-up studies with mice with a human form of CML, AMN107 produced lengthier remissions than Gleevec and triggered remissions in animals in which the disease had become resistant to Gleevec. Side effects in the animals were minimal.

Synthesized in August 2002, AMN107 entered early Phase I clinical studies in May 2004 – 21 months later. Data presented last December at the American Society of Hematology showed that AMN107 had demonstrated significant clinical activity in the most challenging setting: Gleevec resistant accelerated and blast crisis CML patients.

"We’re very encouraged by the results so far," remarks Griffin, who is also a professor of medicine at Harvard Medical School. "This is an elegant example of how rational drug design –– developing drugs based on a molecular understanding of cell structures and processes –– can be used to attack human diseases."

The findings contribute to a larger Dana-Farber research effort, dubbed the "Kinase Project," which seeks to identify abnormal tyrosine kinases -- enzymes that spark or halt growth -- in cancer cells and test agents known to act against them.

The Cancer Cell study’s lead author is Ellen Weisberg, PhD, of Dana-Farber. Co-authors include researchers at Dana-Farber, Novartis, Brigham and Women’s Hospital, and Children’s Hospital Boston.

Bill Schaller | EurekAlert!
Further information:
http://www.danafarber.org

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>