Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

15.02.2005


Hybrid targeted therapy effective in treating Gleevec-resistant disease



Using rational drug design strategies, investigators at Dana-Farber Cancer Institute and Novartis Pharmaceuticals in Basel, Switzerland have created a targeted therapy for chronic myelogenous leukemia (CML) that may ultimately be more effective than Gleevec®, the current frontline treatment. 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.

"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. "The goal of this study was to develop a drug that hits the same target on CML cells as Gleevec does, and to hit more of the target."


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, takes a long time to induce remissions, and patients can develop a resistant type of Bcr-Abl that no longer binds to Gleevec at all.

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.

The final product was AMN107, a half-new, half-old hybrid. Half of AMN107’s chemical makeup is identical to a portion of Gleevec, the remainder is completely different, explains Griffin, who is also a professor of medicine at Harvard Medical School.

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. "In these pre-clinical tests, the new drug was very impressive," says Griffin. "We’ve been able to expand on what we learned from Gleevec to produce a therapy that, thus far, has a more powerful and enduring impact against CML."

AMN107 has been started in early phase clinical trials at M.D. Anderson Cancer Center, and if it proves safe to administer, will be tested for effectiveness in CML patients at Dana-Farber and other sites. If the drug is effective, the next task will be to determine the optimal way of using it –– whether alone or in combination with Gleevec or as a follow-up to Gleevec. Studies are also under way to learn whether AMN107 is effective against other diseases, such as gastrointestinal stromal tumor (GIST), for which Gleevec has become a reliable treatment. "We’re very encouraged by the results so far," Griffin remarks. "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.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>