1916571-90-8

Usage

Uses

Used in Pharmaceutical Industry:
NCT-503 is used as an inhibitor for targeting 3-phosphoglycerate dehydrogenase (PHGDH) in cancer cells. Its application is particularly relevant for the treatment of PHGDH-dependent MDA-MB-468 cancer cells, as it has shown to effectively reduce serine synthesis and suppress tumor growth.
Used in Cancer Research:
NCT-503 is used as a research tool for studying the role of PHGDH in cancer cell metabolism and the potential therapeutic benefits of inhibiting this enzyme. This application aids in understanding the underlying mechanisms of cancer cell growth and the development of novel cancer treatments.
Used in Drug Development:
NCT-503 serves as a starting point for the development of new drugs targeting PHGDH-dependent cancers. Its effectiveness in reducing serine synthesis and suppressing tumor growth makes it a promising candidate for further research and development in the field of oncology.

Biochem/physiol Actions

NCT-503 is an inhibitor of phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first, rate-limiting step of glucose-derived serine synthesis. NCT-503 reduced glucose-derived serine production and suppressed the growth of both PHGDH-dependent cancer cells in culture and in xenograft tumors, and caused G1/S cell cycle arrest in MDA-MB-468 cells. NCT-503 reduced the incorporation of one-carbon units from glucose-derived and exogenous serine into nucleotides, which may contribute to its anticancer activity. NCT-503 had an IC50 value of 2.5 μM for PHGDH and was inactive against a panel of other dehydrogenases and minimal cross-reactivity in a panel of 168 G-protein-coupled receptors (GPCRs). NCT-503 was found to be noncompetitive with respect to both 3-PG and NAD+, and exhibit good stability (>98% after 48 hrs in assay buffer) and aqueous solubility.

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].

IC 50

2.5 μm for inhibiting serine synthesis from 3-phosphoglycerate in cells

references

[1] pacold, m. e.,brimacombe, k.r.,chan, s.h., et al. a phgdh inhibitor reveals coordination of serine synthesis and one-carbon unit fate. nature chemical biology 12(6), 452-458 (2016).