NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor (IC50=2.5 µM) with no activity against other dehydrogenases. NCT-503 has antitumor activity and inhibits the growth of PHGDH-dependent tumors.

PHGDH:2.5 μM

METHODS: Mouse bone marrow cells (BMC) transformed with MLL-AF9 and Hoxa9/Meis1 (HM-2) were treated with MI-503 (0-5 µM) for 7 days, and viability was measured by MTT assay.
RESULTS: Treatment of MLL-AF9 oncogene-transformed BMC with MI-503 resulted in significant growth inhibition, with a GI50 value of 0.22 µM measured after 7 days of treatment.[1]
METHODS: AGS cells overexpressing wild-type menin and three mutant proteins were treated with MI-503 (1 µmol/L) for 48 h. The expression levels of target proteins were detected by Western Blot.
RESULTS: MI-503 increased the expression of nuclear proteins, with the greatest effect observed in R516fs and E235K mutants. [2]

METHODS: To test the in vivo antitumor activity, MI-503 (60 mg/kg, 25% DMSO+25% PEG400+50% PBS) was administered intraperitoneally to BALB/c nude mice bearing MV4;11 xenografts once a day for 20 days.
RESULTS: MI-503 strongly inhibited tumor growth, and treatment with MI-503 resulted in more than 80% reduction of MV4;11, and complete regression of tumor volume and tumor in two mice. [1]

Animal Models: NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotropic xenograftsFormulation: 5% ethanol, 35% PEG 300, and 60% of an aqueous 30% hydroxypropyl-β-cyclodextrin solutionDosages: 40 mg/kgAdministration: i.p.(Only for Reference)