NCT-503

Catalog No.S8619 Batch:S861902

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Technical Data

Formula

C20H23F3N4S
Molecular Weight 408.48 CAS No. 1916571-90-8
Solubility (25°C)* In vitro DMSO 82 mg/mL (200.74 mM)
Ethanol 41 mg/mL (100.37 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 (from reference)

Animal Study:

[1]
  • Animal Models

    NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotropic xenografts

  • Dosages

    40 mg/kg

  • Administration

    i.p.

Selleck's NCT-503 has been cited by 10 publications

Aberrant regulation of serine metabolism drives extracellular vesicle release and cancer progression [ Cell Rep, 2024, 43(8):114517] PubMed: 39024098
PHGDH is Key to a Prognostic Multigene Signature and a Potential Therapeutic Target in Acute Myeloid Leukemia [ J Cancer, 2024, 15(9):2538-2548] PubMed: 38577610
Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells [ Drug Resist Updat, 2023, 70:100985] PubMed: 37423117
PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma [ Nat Commun, 2023, 14(1):1011] PubMed: 36823188
Eubacterium rectale Improves the Efficacy of Anti-PD1 Immunotherapy in Melanoma via l-Serine-Mediated NK Cell Activation [ Research (Wash D C), 2023, 6:0127] PubMed: 37223471
Glutamine and amino acid metabolism as a prognostic signature and therapeutic target in endometrial cancer [ Cancer Med, 2023, 10.1002/cam4.6256] PubMed: 37387559
PERK is a critical metabolic hub for immunosuppressive function in macrophages [ Nat Immunol, 2022, 23(3):431-445] PubMed: 35228694
Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway [ Nat Commun, 2022, 13(1):2698] PubMed: 35577785
Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation [ Oxid Med Cell Longev, 2021, 2021:4232704] PubMed: 34712382
A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer [ Elife, 2020, 9e56749] PubMed: 33016874

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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