The study, reported November 30 in PLoS Computational Biology relates to a class of drugs known as Select Estrogen Receptor Modulators (SERMs), which includes tamoxifen, the most prescribed drug in the treatment of breast cancer.
Unexpected side effects account for one-third of all drug development failures and result in drugs being pulled from the market. Typically drugs are tested using an experimental method which aims to identify off-target proteins that cause side effects. The team in this study, led by Drs. Philip Bourne and Lei Xie, propose a computational modeling approach. If broadly successful the approach could shorten the drug development process and reduce costly recalls.
Rather than considering a single human protein to which a very large number of potential small molecule drugs can bind, Bourne et al. take a single drug molecule and look for how it might bind to as many of the proteins encoded by the human proteome as possible.
The team uses a case study focusing on SERMs to illustrate their technique. They report a previously unidentified protein target for SERMs which is supported by both biochemical and clinical data with known patient outcomes. The identification of a secondary binding site with adverse effects opens the door to changing the drug to maintain binding to the intended target, but to reduce binding to the off-target. This work is just the beginning of the process and experimental validation is continually needed.
By identifying new binding sites the computer analysis may also contribute to repositioning existing drugs to treat completely different diseases from those originally intended. Bourne and Xie are now working in this direction.
Andrew Hyde | alfa
Do microplastics harbour additional risks by colonization with harmful bacteria?
05.04.2018 | Leibniz-Institut für Ostseeforschung Warnemünde
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy