A novel modulator of the de-novo NAD+ biosynthesis.
α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is a critical enzyme in de novo NAD+ biosynthesis from dietary tryptophan. Dysregulation of de novo NAD+ biosynthesis with a consequent NAD+ decline may occur in liver, kidneys and macrophages in various pathological conditions such as NALFD/NASH, Acute Kidney Injury (AKI) and acute inflammation respectively.
We have developed small molecule inhibitors of ACMSD that provides a novel way to re-establish NAD+ homeostasis and prevent depletion of NAD+ levels caused by an increased energy demands in pathophysiological conditions.
Our lead compound is highly effective both in vitro and in vivo in increasing de novo NAD+ biosynthesis in a range of preclinical models of reduced NAD+ supply and/or perturbed NAD+ homeostasis such as Acute Kidney Injury, NAFLD/NASH, and acute inflammation.