| Identification | Back Directory | [Name]
NCT-503 | [CAS]
1916571-90-8 | [Synonyms]
NCT-503
CS-2612
NCT 503;NCT503
NCT-503 >=98% (HPLC)
NCT-503; NCT 503; NCT503.
1-Piperazinecarbothioamide, N-(4,6-dimethyl-2-pyridinyl)-4-[[4-(trifluoromethyl)phenyl]methyl]-
9-(6-aminopyridin-3-yl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one | [Molecular Formula]
C20H23F3N4S | [MDL Number]
MFCD30343875 | [MOL File]
1916571-90-8.mol | [Molecular Weight]
408.48 |
| Hazard Information | Back Directory | [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.1 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.1 | [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). |
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| Company Name: |
BOC Sciences
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| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
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