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
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences