MTHFD2 inhibitor - Inflammation auto-immune diseases

"MTHFD2 is a mitochondrial enzyme involved in the folate-mediated one-carbon metabolism pathway. It plays a crucial role in controlling the fate and function of Th17 cells, and its inhibition promotes a Treg cell-like phenotype.

MTHFD2 deficiency has been shown to reduce disease severity in multiple in vivo inflammatory disease models. Pharmacological inhibition of MTHFD2 has the potential to treat various inflammatory conditions with an improved safety profile compared to Methotrexate or JAK inhibitors.

We have applied our AI-driven drug discovery platforms, Makya and Spaya, to identify novel, potent, and selective MTHFD2 inhibitors. IKT-001432, a representative molecule from our lead series, is a potent (IC50 < 10nM) and potential first-in-class MTHFD2 inhibitor with desirable drug-like properties. Preclinical candidate nomination is expected early 2026."