The research findings were published April 13 in the journal Cancer Cell. Professors Alexander MacKerell Jr., PhD, and Andrew Coop, PhD, MA, researchers at UMB's Computer-Aided Drug Design (CADD) Center, part of the School of Pharmacy, discovered a small molecule that decouples proteins that contribute to a form of cancer known as diffuse large B-cell lymphoma (DLBCL). The type accounts for as much as 30 percent of newly reported cases of lymphoma.
"This discovery indicates that a small molecule has the potential to be a therapeutic for a very common form of non-Hodgkin lymphoma, which is presently very difficult to treat," said Coop, chair of the School's Department of Pharmaceutical Sciences. "It has huge potential for cancer therapy."
At the CADD Center, of which he is director, MacKerell and team members directed specially designed computer models to find among millions of chemicals those most likely to disrupt protein-to-protein interactions thought to contribute to DLBCL. From about 200 candidates selected from the screen, several - including one labeled simply 79-6 - were identified to inhibit DLBCL. In the laboratories of collaborators Ari Melnick, MD, associate professor, Weill Cornell Medical College, and Gil Privý, PhD, professor, University of Toronto, experiments revealed that 79-6 was nontoxic in animal experiments and could kill human lymphoma cells.
MacKerell said, "We were able to find a small molecule that inhibited the interaction of a transcriptional factor called B-cell lymphoma protein [BCL6] and its partner proteins, which was then shown by our collaborators to be a potential treatment for DLBCL." Transcriptional factor proteins read and interpret the genetic "blueprint" in the DNA, and scientists have associated the BCL6 transcriptional factor with development of large cell lymphomas.
Because the discovery delved into the intimacy of interactions between proteins involved in transcription, MacKerell added, "I think the discovery may lead to a new category of cancer treatments."
The collaboration was typical of CADD efforts in drug discovery studies, the co-authors said. The Center was formally created in 2001 to foster collaborative research among biologists, biophysicists, structural biologists, and computational scientists. The goal is to initiate these collaborations, in turn leading to research projects to discover chemical entities with the potential to be developed into novel therapeutic agents.
According to the Lymphoma Research Foundation Web site, there are more than 60 non-Hodgkin's lymphomas (NHLs). Of these, it says of DLBCL, "Large cell lymphomas are the most common type of lymphoma, comprising about 30 percent (to) 40 percent of NHLs. The median age of those affected is 57, with a range of 10 to 88 years. Although most frequently seen in adults, large cell lymphomas may also be seen in children. These aggressive cancers may arise in lymph nodes or in extranodal sites, including the gastrointestinal tract, testes, thyroid, skin, breast, central nervous system or bone."
Steve Berberich | Newswise Science News
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering