TITLE:
Toxicology and Applied Pharmacology Preclinical Safety Evaluation of SPRC, a Novel H2S Donor, in Rats
AUTHORS:
XianLiang He, Wei Qi, Rinkiko Suguro, Sei Suguro, Chen Fan
KEYWORDS:
S-Propargyl-Cysteine, Hydrogen Sulfide, No-Observed Adverse Effect Level, Therapeutic Window, Safety
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.18 No.5,
May
27,
2025
ABSTRACT: Hydrogen sulfide (H2S) is a crucial signaling molecule involved in regulating inflammation, oxidative stress, and metabolism. S-propargyl-cysteine (SPRC) modulates endogenous H2S production pathways by influencing relevant enzymes, presenting a potential therapeutic approach for conditions associated with abnormal sulfide levels. This study investigated the safety and pharmacokinetic properties of SPRC in a Good Laboratory Practice 28-day oral toxicity study in rats, including safety pharmacology and gene toxicity assessments. SPRC exhibited favorable pharmacokinetic characteristics and safety margins, with a No Observed Adverse Effect Level (NOAEL) of 37.5 mg/kg, translating to an estimated 8.5-fold therapeutic window. These initial toxicology findings, coupled with SPRC’s pharmacological effects on the sulfide signaling axis, support its progression to first-in-human clinical trials for further benefit risk evaluation. The promising safety and pharmacokinetic profile of SPRC underscores its therapeutic potential and justifies additional clinical investigation for disorders linked to aberrant sulfide signaling. To comprehensively assess the therapeutic utility of SPRC, further preclinical safety evaluations and early phase clinical studies are warranted. These investigations will provide insights into SPRC’s potential to address unmet medical needs in various disease areas related to disrupted sulfur metabolism and hydrogen sulfide biology.