1916571-90-8

Basic information

• Product Name: NCT-503
• Synonyms: NCT-503
• CAS NO: 1916571-90-8
• Molecular Formula: C20H23F3N4S
• Molecular Weight: 408.4836296
• Mol File: 1916571-90-8.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• Solubility: ≥40.9 mg/mL in DMSO; insoluble in H2O; ≥20.33 mg/mL in EtOH
• CAS DataBase Reference: NCT-503(CAS DataBase Reference)
• NIST Chemistry Reference: NCT-503(1916571-90-8)
• EPA Substance Registry System: NCT-503(1916571-90-8)

Safety Data

• Hazardous Substances Data: 1916571-90-8(Hazardous Substances Data)

Usage

Description

NCT-503 is an inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), inhibiting serine synthesis from 3-phosphoglycerate in cells with an IC50 value of 2.5 μM. It has been shown to reduce the production of glucose-derived serine in cells and to suppress the growth of PHGDH-dependent MDA-MB-468 cancer cells both in vitro and in mice bearing orthotopic xenograft tumors.

Uses

NCT-503 is a novel inhibitor of human Phosphoglycerate Dehydrogenase (PHGDH).

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).