Unmet Need
Hydrogen sulfide (H2S) has long been studied as an endogenous signaling molecule responsible for a variety of bodily functions including inhibition of inflammation, inhibition of oxidative stress and regulation of calcium and pH levels in brain cells (anti-Parkinson’s Disease). In addition, liver and ovarian cancer cells have been shown to produce increased amounts of H2S. However the role of H2S and mechanism of action in these bodily functions is unclear to date. Recently, it has been reported that some of the activity that has been attributed to H2S may be attributed to hypersulfides (RSSH) or polysulfides (RSnR). Classical methods of producing hypersulfides are done in non-physiological conditions. In order to study the role of hypersulfides in these bodily functions, the hypersulfides must be producible in situ and the rate of release of the active hypersulfide must be controllable under physiological conditions. Furthermore, any RSSH prodrugs developed would require the same parameters, in addition to being bench stable for some period of time.
Technology Overview
Johns Hopkins researchers have created a class of chemical compounds (S-Substituted Thioisothioureas) that are precursors to hypersulfides that can will release RSSH under physiological conditions. These researchers have shown that hypersulfides with a variety of functional groups can be produced in situ using this chemistry. With the ability to produce these compounds in situ in a physiological environment, research can be done to determine the role that RSSH has in bodily functions, and possible therapeutic and/or drug targets may be designed for many of the ailments listed above which utilize the S-substituted thioisothiourea functional group. Additionally, these precursors are bench stable as a solid for several months.
Stage of Development
The researchers thus far have shown that RSSH can be released reliably and controllably with a variety of substituent “R” groups. Further development of this class of compounds and evaluation of their biological properties is ongoing.
Publication
Khodade VS, Toscano JP. Development of S-Substituted Thioisothioureas as Efficient Hydropersulfide Precursors. J. AM. Chem. Soc. 2018, 140, 50, 17333-17337
