Novel activator drugs to deliver hydrogen sulfide therapy
A successful drug development consortium based in the North Netherlands recently embarked on a new project to discover new drugs that have the unique property of activating enzymes that produce the gas hydrogen sulfide (H2S). The consortium is led by the UMCG department of Clinical Pharmacy and Pharmacology, and includes partners from Drug Design of the University of Groningen and industry, namely the biotech company Sulfateq, and chemistry experts from Symeres.
Currently, there is a critical gap in innovation for the treatment of Alzheimer’s disease, a condition which suffers from reduced levels of H2S. This gas is important for oxidative defense and mitochondrial function. In addition, the same problem is now known for diabetes and cardiovascular diseases. Importantly, the above mentioned diseases are on the WHO list of top 10 globally leading causes of death. With the proposed innovative therapy, the patient will be stimulated to produce more of their own H2S to improve the disease conditions and healthy aging.
To find such new drugs, this consortium first developed a firm understanding of the molecular mechanism of activation. Using virtual models of the target enzyme, they already screened millions of compounds on the university supercomputer and selected the most promising candidates. In addition, thousands of compounds will be tested in our lab directly on recombinant enzyme. They also designed their own new chemicals and are in the process of synthesis and testing. Working activators will be validated in cells and animals, and submitted in a patent application. The innovative drug discovery of activator drugs will be documented in a scientific publication that can improve the development of novel therapies for global diseases. Finally, in the future the consortium aims to advance the lead compounds into clinical trials.
