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
Reptile vocalization is surprisingly flexible
30.05.2017 | Max-Planck-Institut für Ornithologie
New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
30.05.2017 | Life Sciences
30.05.2017 | Power and Electrical Engineering
29.05.2017 | Earth Sciences