Dihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic Diseases

Despite the current FDA approved therapiesthe prevalence of typediabetesT Dand various other metabolic diseases is reaching epidemic proportionsGloballymillion people have overt diabetesand the prevalence of impaired fasting glucoseprecursor to T D referred to aspre diabetesisof the US populationConsequentlyT D and its frequent co morbiditieshigh triglyceridesnon alcoholic fatty liver diseasenon alcoholic steatohepatitisNAFLD NASHand cardiovascular diseaseincreasingly account for a large proportion of global end stage renal and liver failurelimb amputationsblindnessmyocardial infarctionsand strokesTo address this highly unmet needPotrero Hill TherapeuticsPHThas discovered highlypotentdrug likeand orally active small molecule inhibitors of dihydroceramide desaturaseDESa key enzyme which catalyzes the final step in the de novo formation of ceramidesmolecules which drive insulin resistancehigh triglyceridesfatty liverand atherosclerosis when produced in excessThis work has been partially funded through an SBIR Phasegrantand in this PhasegrantPHT will continue preclinical characterization and early development of its lead DESinhibitor candidateWe will comprehensively profile the therapeutic activity of our lead DESinhibitor candidate in a well validated mouse model of insulin resistance T Dand compare its potency to those of several other candidate DESinhibitorsWe will conduct pilot safety studies of our most potent DESinhibitor candidate in order to determine safety margins and identify potential off target activitiesandWe will continue medicinal chemistry to generate several backup DESinhibitorsUltimatelysuccessful completion of these aims will yield a clinical development candidate that is ready for IND enabling activitiesincluding GMP manufacturing and pivotal GLP toxicology safety studiespaving the way for clinical trials in humans Despite the current FDA approved therapiesthe increasing prevalence of typediabetesand various other metabolic diseases of insulin resistanceis reaching epidemic proportionsGloballymillion have overt diabetesand the prevalence of impaired fasting glucoseprecursor to typediabetes referred to aspre diabetesisof the US populationPotrero Hill Therapeutics is developing a novel class of therapeutics to treat diabetesabnormal blood lipidse ghigh triglyceridesfatty liverand various other diseases