New therapeutic target identified for diseases caused by lack of oxygen
<p>The study, in which the University of Barcelona is participating, is a new approach to ischemic injuries and anemia</p>
An international team of scientists has developed a new therapeutic approach to ischemic injuries of the brain or heart caused by a lack of blood flow, as well as cardiovascular accidents and anemia caused by chronic kidney failure or chemotherapy.
The paper, published in Nature Communications and signed by first authors Carles Galdeano (Beatriu de Pinós researcher at the University of Barcelona) and Julianty Frost (of the University of Dundee, United Kingdom), discusses a new small-molecule probe –VH298– they have developed that causes a controlled hypoxic response inside cells.
This molecule could inhibit protein-protein interaction between the E3 ubiquitin ligase VHL and the HIF-1α transcription factor, a process that triggers a set of similar processes, in a totally selective and controlled manner, in cells under hypoxic conditions, meaning those lacking oxygen.
According to Carlos Galdeano, the work verifies “for the first time” that the E3 ligase VHL protein can be modified with drugs and that VH298 is able to boost erythropoietin hormone levels (EPO) in cells, increasing the number of red blood cells, which transport oxygen. The research was led by Alessio Ciulli, a researcher at the University of Dundee.
There is growing interest in using small-molecule probes to create new drugs because it allows researchers to chemically validate new pharmacological targets in a highly selective manner and come up with chemical compounds that can quickly be developed as drugs. The difficulty lies in successfully identifying and developing these small-molecule probes.
Related publication:
- Potent and selective chemical probe of hypoxic signaling downstream of HIF-α hydroxylation via VHL inhibition. Nature Communications 7 (04 November 2016) doi:10.1038/ncomms13312