Novel activator drugs to deliver hydrogen sulfide therapy

Allosteric activators of cystathionine-β-synthase as novel therapeutic agents providing 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, including the biotech company Sulfateq, and chemistry experts from Symeres.

Currently, there are critical gaps in innovation for the treatment of Alzheimer’s disease diabetes and cardiovascular diseases, conditions which suffer from reduced levels of H2S. This gas is important for defense against highly reactive oxygen species and mitochondrial function. 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, the consortium first developed a firm understanding of the molecular mechanism of activation. Using computer 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 their lab directly on purified enzyme. They also designed their own new chemicals and are in the process of synthesis and testing these. 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.

This drug discovery project aims to improve treatment of diseases including Alzheimer’s, diabetes, and cardiovascular. Deficient hydrogen sulfide production in these diseases is associated with oxidative stress and impaired signaling. Novel activating drugs will stimulate the organism to produce more own hydrogen sulfide, improve the clinical condition and healthy aging.
Technology Readiness Level (TRL)
5 - 7
Time period
36 months