NCT-503

Catalog No.S8619

NCT-503 Chemical Structure

Molecular Weight(MW): 408.48

NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with the IC50 value of 2.5 μM. It is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity in a panel of 168 GPCRs.

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Biological Activity

Description NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with the IC50 value of 2.5 μM. It is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity in a panel of 168 GPCRs.
Targets
PHGDH [1]
(Cell-free)
2.5 μM
In vitro

NCT-503 has reasonable aqueous solubility, and exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties[1]. NCT-503 selectively blocks glucose-derived serine synthesis but at the same time triggers SHMT1-dependent one-carbon unit wasting to synthesize serine from glycine. This futile cycle depletes the cell of nucleotides and leads to cell cycle arrest[2].

In vivo NCT-503 has good exposure (AUClast=14,700 hr*ng/mL), half-life (2.5 hr) and Cmax (~20 µM in plasma) following intraperitoneal administration with significant partitioning into the liver and brain. PHGDH inhibition by NCT-503 selectively increases necrosis in MDA-MB-468 xenografts, but not in MDA-MB-231 xenografts. It also reduces the growth and weight of PHGDH-dependent MDA-MB-468 xenografts but does not affect the growth or weight of PHGDH-independent MDA-MB-231 xenografts[1].

Protocol

Animal Research:

[1]

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  • Animal Models: NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotropic xenografts
  • Formulation: 5% ethanol, 35% PEG 300, and 60% of an aqueous 30% hydroxypropyl-β-cyclodextrin solution
  • Dosages: 40 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 81 mg/mL (198.29 mM)
Ethanol 81 mg/mL (198.29 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 408.48
Formula

C20H23F3N4S

CAS No. 1916571-90-8
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Dehydrogenase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID