NCT-503 Struktur

NCT-503

Bezeichnung:NCT-503

CAS-Nr1916571-90-8

Englisch Name:NCT-503

CBNumberCB83159381

SummenformelC20H23F3N4S

Molgewicht408.48

MOL-Datei1916571-90-8.mol

NCT-503 physikalisch-chemischer Eigenschaften

Siedepunkt	474.3±55.0 °C(Predicted)
Dichte	1.306±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	≥40.9 mg/mL in DMSO; insoluble in H2O; ≥20.33 mg/mL in EtOH
Aggregatzustand	powder
pka	12.99±0.20(Predicted)
Farbe	white to beige

Gefahreninformationscode (GHS)

NCT-503 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Verwenden
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
Einzelnachweise
[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).

NCT-503 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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