TES Pharma has developed the first potent and selective class of ACMSD inhibitors

α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), is a critical enzyme in de novo NAD+ biosynthesis.  As an upstream event in NAD+ biosynthesis from tryptophan, inhibition of ACMSD thus has significant advantages in controlling NAD+ levels by channelling the kynurenine pathway towards de novo NAD+ synthesis. ACMSD inhibitors provide a novel way to to re-establish NAD+ homeostasis and prevent depletion of NAD+ levels caused by an increased energy demands in pathophysiological conditions.  Since the efficiency of the kynurenine pathway in producing de novo NAD+, is primarily determined by the activity of ACMSD.

TES Pharma has developed the first potent and selective class of ACMSD inhibitors.  Our lead compound TES-1025 is highly effective in vitro and in vivo in increasing NAD+ biosynthesis.

Our ACMSD inhibitors are being progressed towards clinical studies for disorders with reduced NAD+ supply and/or perturbed NAD+ homeostasis, in particular for Acute Kidney Injury and NASH.  Both disease areas have significant and pressing medical need.

Our lead compounds derive from a long-standing and successful expertise in identifying novel modulators of key targets in the kynurenine pathway.

• R Pellicciari et al., J. Med. Chem 2018, Jan 26, “Novel Inhibitors of ACMSD for NAD+ Biosynthesis”
• US9,708,272(B2), “Inhibitors of ACMSD”, TES Pharma
• US2017/362,185(A1), “Inhibitors of ACMSD”, TES Pharma