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Overview
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Background
IC50: 2.5 μM for inhibiting serine synthesis from 3-phosphoglycerate in cells
NCT-503 is a 3-phosphoglycerate dehydrogenase (PHGDH) inhibitor.
In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) has been reported to catalyze the first, rate-limiting step.
In vitro: NCT-503 was identified as an inhibitor of PHGDH and was found to be inactive against a panel of other dehydrogenases and showed minimal cross-reactivity in a panel of G-protein-coupled receptors. In addition, treatment of three PHGDH-independent cell lines and five PHGDHdependent cell lines with NCT-503 demonstrated that NCT-503 had EC50 values of 8–16 μM for the PHGDH-dependent cell lines, and no toxicity toward other PHGDH-independent cell lines [1].
In vivo: To evaluate NCT-503 in-vivo activity, NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotopic xenografts were treated with vehicle or NCT-503. Results showed that NCT-503 treatment reduced the growth and weight of PHGDH-dependent xenografts but did not affect those of PHGDH-independent xenografts. Importantly, mice treated with NCT-503 did not lose weight during the 24-d treatment in spite of the potential systemic toxicities of inhibiting serine biosynthesis [1].
Clinical trial: So far, no clinical study has been conducted.
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