NCT-503

製品コードS8619 バッチS861901

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₀H₂₃F₃N₄S

分子量

408.48

CAS No.

1916571-90-8

Solubility (25°C)*

体外

DMSO

81 mg/mL (198.29 mM)

Ethanol (warmed with 50ºC water bath)

20 mg/mL (48.96 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%Ethanol 1 40%PEG300 2 5%Tween80 3 50%ddH2O

1.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL 20 mg/ml clarified Ethanol stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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].

製品説明

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.

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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Cell-free assays
	濃度	2.5 μM
	反応時間
	実験の流れ
動物実験	動物モデル	NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotropic xenografts
	投薬量	40 mg/kg
	投与方法	i.p.

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。