| Identification | Back Directory | [Name]
NCT-502 | [CAS]
1542213-00-2 | [Synonyms]
N-(4
NCT-502
6-dimethylpyridin-2-yl)-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbothioamide
N-(4,6-dimethylpyridin-2-yl)-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbothioamide
1-Piperazinecarbothioamide, N-(4,6-dimethyl-2-pyridinyl)-4-[5-(trifluoromethyl)-2-pyridinyl]- | [Molecular Formula]
C18H20F3N5S | [MOL File]
1542213-00-2.mol | [Molecular Weight]
395.45 |
| Chemical Properties | Back Directory | [Boiling point ]
512.3±60.0 °C(Predicted) | [density ]
1.355±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≤30mg/ml in ethanol;30mg/ml in DMSO;30mg/ml in dimethyl formamide | [form ]
solution in methanol. | [pka]
12.95±0.20(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
NCT-502 is a novel inhibitor of human Phosphoglycerate Dehydrogenase (PHGDH). | [Definition]
ChEBI: N-(4,6-dimethyl-2-pyridinyl)-4-[5-(trifluoromethyl)-2-pyridinyl]-1-piperazinecarbothioamide is a member of piperazines and a member of pyridines. | [Biological Activity]
nct-502 is an inhibitor of 3-phosphoglycerate dehydrogenase (phgdh).serine, a proteinogenic amino acid, is the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. homo sapiens phosphoglycerate dehydrogenase (phgdh) catalyzes the first, rate-limiting step in the canonical pathway of glucose-derived serine synthesis. | [in vitro]
nct-502 was identified as an inhibitor of 3-phosphoglycerate dehydrogenase (phgdh), inhibiting serine synthesis from 3-phosphoglycerate in cells. nct-502 was inactive against a panel of other dehydrogenases and showed minimal cross-reactivity in a panel of 168 g-protein-coupled receptors. moreover, in mda-mb-231-phgdh cells, nct-502 treatment could decrease the intracellular serine and glycine concentrations and did not change the concentration of any other amino acid except for aspartate. in addition, nct-502-mediated inhibition of serine synthesis was found to be reversible in cells [1]. | [in vivo]
to evaluate the in-vivo activity nct-503, a structurally close analog of nct-502, 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 reduced the growth and weight of phgdh-dependent mda-mb-468 xenografts but did not affect those of phgdh-independent mda-mb-231 xenografts. phgdh inhibition caused by nct-503 also selectively increased necrosis in mda-mb-468 but not mda-mb-231 xenografts. importantly, mice treated with nct-503 did not lose weight during the 24-d treatment [1]. | [IC 50]
3.7 μm | [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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