AR9281 / Arete - LARVOL DELTA

A New Family of Subnanomolar inhibitors of Soluble Epoxide Hydrolase. (PubMed, FASEB J) - "Although several potent sEH inhibitors (sEHI) have been developed, including clinical candidates AR9281, GSK2256294, and EC5026, so far no sEHI has reached the market. Biol. 2020, 1274, 71-99."

Journal • Inflammation • Pain

Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis. (PubMed, Eur J Med Chem) - "Molecular docking displayed that 3,5-dimethyl on the adamantyl group in B401 could make van der Waals interactions with residues at a hydrophobic pocket of sEH active site, which might indirectly explain the subnanomolar level activities of memantyl urea derivatives in vitro better than AR-9281...Although the median survival time of C57BL/6 mice in LPS-induced sepsis model was slightly increased, the survival rate did not reach significant efficacy. Based on safety profile, metabolic stability, pharmacokinetic and in vivo efficacy, B401 demonstrated the proof of potential for this class of memantyl urea-based sEH inhibitors as therapeutic agents in sepsis."

Journal • Immunology • Infectious Disease • Inflammation • Septic Shock • Systemic Inflammatory Response Syndrome • EPHX1

From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis. (PubMed, J Med Chem) - "Numerous potent sEH inhibitors (sEHIs) present adamantyl or phenyl moieties, such as the clinical candidates AR9281 or EC5026. A screening cascade permitted us to select a candidate for an in vivo efficacy study in a murine model of cerulein-induced acute pancreatitis. The administration of 22 improved the health status of the animals and reduced pancreatic damage, demonstrating that the benzohomoadamantane unit is a promising scaffold for the design of novel sEHIs."

Journal • Preclinical • Pain • Pancreatitis • EPHX1

PET imaging of soluble epoxide hydrolase in non-human primate brain with [F]FNDP. (PubMed, EJNMMI Res) - "[F]FNDP is a highly sEH-specific radiotracer that is suitable for quantitative PET imaging in the baboon brain. [F]FNDP holds promise for translation to human subjects."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Depression • Gene Therapies • Movement Disorders • Parkinson's Disease • EPHX1