NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC₅₀ of 2.5 µM.

IC50: 2.5 µM (PHGDH)^[1]

Human phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step in the canonical glucose-derived serine synthesis pathway. NCT-503, a PHGDH inhibitor, inhibits serine synthesis from 3-phosphoglycerate in cells (IC₅₀=2.5 µM). NCT-503 is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity in a panel of 168 GPCRs. Competition studies of NCT-503 against 3-phosphoglycerate (3-PG) and the co-substrate NAD⁺ reveal a non-competitive mode of inhibition with respect to both 3-PG and NAD⁺. NCT-503 has EC₅₀s of 8–16 µM for the PHGDH-dependent cell lines, a 6- to 10-fold higher EC₅₀ for MDA-MB-231 cells, and no toxicity towards other PHGDH-independent cell lines^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

NCT-503 exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties. NCT-503 has good exposure, half-life (2.5 hr) and C_max (20 µM in plasma) following intraperitoneal administration with significant partitioning into the liver and brain. NCT-503 treatment 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

408.48

C₂₀H₂₃F₃N₄S

1916571-90-8

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL (122.41 mM; Need ultrasonic)

Ethanol : 13.33 mg/mL (32.63 mM; ultrasonic and warming and heat to 60°C)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: 2.5 mg/mL (6.12 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (6.12 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.12 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.12 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• 3.

  请依序添加每种溶剂： 0.5% methylcellulose    0.2% Tween 80

  Solubility: 2 mg/mL (4.90 mM); Suspended solution; Need ultrasonic

• [1]. Pacold ME, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8.

MDA-MB-468, BT-20, MT-3 cells are seeded in white 96-well plates allowed to attach for 24 hours. Cells are treated with NCT-503 for four days. Cell viability is assessed with Cell Titer-Glo and luminescence measured with a plate reader^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice: Chronic catheters are surgically implanted into the jugular veins of normal or tumor bearing animals 3-4 days prior to infusions. Following administration of either vehicle or NCT-503 at 30 mg/kg, a constant infusion of U-¹³C-glucose (30 mg/kg/min) is administered for a 3-hour duration. Animals are terminally anesthetized with sodium pentobarbital and all tissues are fully harvested in less than 5 minutes to preserve the metabolic state. Tumors and adjacent lung tissue are carefully dissected and rapidly frozen for analysis^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Pacold ME, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8.