2. Metabolic Enzyme/Protease
  3. Phosphoglycerate Dehydrogenase (PHGDH)
  4. NCT-503

NCT-503 is a blood-brain barrier-permeable, non-competitive PHGDH inhibitor with an IC50 of 2.5 μM against human PHGDH. NCT-503 reduces glucose-derived serine production and the incorporation of one-carbon units into nucleotides without decreasing PHGDH protein expression. NCT-503 prevents high selenium-induced insulin resistance in mice by regulating blood glucose and insulin levels and improving glucose tolerance, and also inhibits the growth of tumors overexpressing PHGDH. NCT-503 can be used in research related to insulin resistance and breast cancer.

For research use only. We do not sell to patients.

CAS No. : 1916571-90-8

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Customer Review

Based on 28 publication(s) in Google Scholar

Other Forms of NCT-503:

NCT-503 Related Antibodies

Top Publications Citing Use of Products
WB
Cell Proliferation/Viability Assay
RT-PCR
In Vivo Efficacy Study

    NCT-503 purchased from MedChemExpress. Usage Cited in: J Virol. 2023 Mar 30;97(3):e0001623.  [Abstract]

    NCT-503 (2.5, 5, 10 µM) blocks serine synthesis but promotes a compensatory upregulation of MTHFD2 in Newcastle disease virus (NDV)-infected cells.

    NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371.  [Abstract]

    SW1990 cells expressing the indicated Flag–c-Jun were pretreated with NCT-503 (40 μM) and were cultured in glucose-free DMEM for 12 h.

    NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371.  [Abstract]

    Cells pretreated with or without NCT-503 (40 μM) were cultured in normal or glucose-free DMEM for 36 h Cellular viability was examined by CCK-8 assay

    NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371.  [Abstract]

    Cells pretreated with or without NCT-503 (40 μM) were cultured in normal or glucose-free DMEM for 24 h. mRNA levels of potential c-Jun target genes were analysed by real-time PCR.

    NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371.  [Abstract]

    A total of 1 × 107 SW1990 cells expressing the indicated sgRNAs were subcutaneously injected into athymic nude mice. NCT-503 (40 mg/kg/day; i.p.) administration in mice 7 d after subcutaneous injection of tumour cells. Representative tumour xenografts (left) and quantification of tumour volumes (middle) are shown; lysates were collected from SW1990 cells that were cultured for 6 h in glucose-free DMEM and from tumour tissues, then immunoprecipitated c-Jun was subjected to immunoblotting analyses (right).

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    NCT-503 is a blood-brain barrier-permeable, non-competitive PHGDH inhibitor with an IC50 of 2.5 μM against human PHGDH. NCT-503 reduces glucose-derived serine production and the incorporation of one-carbon units into nucleotides without decreasing PHGDH protein expression. NCT-503 prevents high selenium-induced insulin resistance in mice by regulating blood glucose and insulin levels and improving glucose tolerance, and also inhibits the growth of tumors overexpressing PHGDH. NCT-503 can be used in research related to insulin resistance and breast cancer[1][2].

    IC50 & Target

    IC50: 2.5 µM (PHGDH)[1]
    Cellular Effect
    Cell Line Type Value Description References
    MDA-MB-231 IC50
    8 μM
    Compound: 31; NCT-503
    Antiproliferative activity against human MDA-MB-231 cells overexpressing PHGDH assessed as reduction in cell growth
    Antiproliferative activity against human MDA-MB-231 cells overexpressing PHGDH assessed as reduction in cell growth
    		[PMID: 39106658]
    MDA-MB-468 EC50
    8 μM
    Compound: 31; NCT-503
    Cytotoxicity against human MDA-MB-468 cells
    Cytotoxicity against human MDA-MB-468 cells
    		[PMID: 29555419]
    In Vitro

    NCT-503 (10 μM; 1 h pretreatment, 4 h/24 h tracer incubation) engages PHGDH in MDA-MB-468 cells, reducing glucose-derived serine synthesis, impairing one-carbon unit incorporation into nucleotides from both endogenous and exogenous serine, and increasing SHMT1-mediated one-carbon unit wasting; the C234S PHGDHG12C mutant reduces NCT-503 potency by ~3-fold[2].
    NCT-503 (dose-response concentrations; 4 days) selectively inhibits the viability of PHGDH-dependent human cancer cell lines (MDA-MB-468, BT-20, HCC70, HT1080, MT-3) with EC50 values of 8-16 μM, while showing minimal to no toxicity towards PHGDH-independent cell lines[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    NCT-503 Related Antibodies

    Cell Viability Assay[2]

    Cell Line: PHGDH-dependent (MDA-MB-468, BT-20, HCC70, HT1080, MT-3) and PHGDH-independent (MDA-MB-231, ZR-75-1, SK-MEL-2) human cancer cell lines
    Concentration: Dose-response concentrations
    Incubation Time: 4 days
    Result: Exhibited EC50 values of 8-16 μM for PHGDH-dependent cell lines.
    Showed a 6- to 10-fold higher EC50 for MDA-MB-231 cells.
    Showed no toxicity towards other PHGDH-independent cell lines.
    In Vivo

    NCT-503 (30 mg/kg; i.p.; twice weekly; 5 months) effectively prevents high-selenium-induced insulin resistance in male C57BL/6J mice, as evidenced by normalized fasting blood glucose, improved glucose tolerance and insulin sensitivity, reduced plasma insulin levels, and restored PI3K-AKT-mTOR pathway activity in pancreatic tissue, while potently inhibiting PHGDH enzyme activity across liver, muscle, and pancreas tissues[1].
    NCT-503 (40 mg/kg; i.p.; daily; 24 days) selectively inhibits growth and induces necrosis in PHGDH-dependent MDA-MB-468 orthotopic breast cancer xenografts in NOD.CB17-Prkdcscid/J mice without causing weight loss[2].
    NCT-503 (30 mg/kg; i.p.; single dose) engages PHGDH in MDA-MB-468 orthotopic xenografts, reducing glucose-derived serine synthesis[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Model: C57BL/6J (male, 4 weeks old, SPF status, high-selenium diet-induced insulin resistance model)[1]
    Dosage: 30 mg/kg
    Administration: i.p.; twice weekly; 5 months
    Result: Significantly reduced high-selenium-induced weight gain compared to the high-selenium alone group, with final body weight closer to the adequate-selenium control group.
    Prevented the gradual increase in fasting blood glucose levels seen in the high-selenium alone group, with levels remaining near those of the adequate-selenium control group by the fifth month.
    Improved glucose tolerance, with significantly lower blood glucose levels compared to the high-selenium alone group during the glucose tolerance test.
    Improved insulin sensitivity, with a reduced percentage change in blood glucose following insulin injection compared to the high-selenium alone group.
    Significantly reduced plasma insulin levels compared to the high-selenium alone group.
    Significantly increased plasma homocysteine levels compared to the high-selenium alone group.
    Significantly reduced plasma serine levels compared to the high-selenium alone group.
    Markedly reduced PHGDH enzyme activity in the liver, muscle, and pancreas compared to the high-selenium alone group; PHGDH activity was also significantly lower than in the adequate-selenium control group and the high-selenium + serine group.
    Significantly reduced GPX1 and SELENOP protein expression in the liver compared to the high-selenium alone group and the high-selenium + serine group.
    Significantly reduced GPX1 and SELENON protein expression in the muscle compared to the high-selenium alone group and the high-selenium + serine group.
    Significantly reduced GPX1 protein expression in the pancreas compared to the high-selenium alone group and the high-selenium + serine group.
    Increased PHGDH protein expression in the liver, muscle, and pancreas compared to the high-selenium + serine group.
    Significantly increased SHMT1 protein expression in the pancreas compared to the high-selenium + serine group.
    Significantly increased mTOR protein expression in the pancreas compared to the high-selenium alone group.
    Significantly increased phosphorylated Akt (Ser-473 and Thr-308) protein expression in the pancreas compared to the high-selenium alone group.
    Animal Model: NOD.CB17-Prkdcscid/J (female, 6-8 weeks old, orthotopic xenograft via injection of 500,000 MDA-MB-468 cells into the 4th mammary fat pad)[2]
    Dosage: 40 mg/kg
    Administration: i.p.; daily; 24 days
    Result: Reduced the growth and weight of PHGDH-dependent MDA-MB-468 xenografts.
    Selectively increased necrosis in these xenografts.
    Decreased production of glucose-derived serine in tumors.
    Reached ~3 μM tumor exposure at the end of the experiment.
    Prevented weight loss in mice during the 24-day treatment period.
    Molecular Weight

    408.48

    Formula

    C20H23F3N4S
    CAS No.
    Appearance

    Solid

    Color

    Off-white to light yellow

    SMILES

    S=C(N1CCN(CC2=CC=C(C(F)(F)F)C=C2)CC1)NC3=NC(C)=CC(C)=C3
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 50 mg/mL (122.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4481 mL 12.2405 mL 24.4810 mL
    5 mM 0.4896 mL 2.4481 mL 4.8962 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

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

      This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

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

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 10 mg/mL (24.48 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  0.5% Methylcellulose/0.2% Tween-80 in Saline water

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

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.69%

    SDS (393 KB)

    COA (244 KB) HNMR (254 KB) RP-HPLC (249 KB) LCMS (93 KB)

    Handling Instructions (2659 KB)
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    Ethanol / DMSO 1 mM 2.4481 mL 12.2405 mL 24.4810 mL 61.2025 mL
    5 mM 0.4896 mL 2.4481 mL 4.8962 mL 12.2405 mL
    10 mM 0.2448 mL 1.2241 mL 2.4481 mL 6.1203 mL
    15 mM 0.1632 mL 0.8160 mL 1.6321 mL 4.0802 mL
    20 mM 0.1224 mL 0.6120 mL 1.2241 mL 3.0601 mL
    25 mM 0.0979 mL 0.4896 mL 0.9792 mL 2.4481 mL
    30 mM 0.0816 mL 0.4080 mL 0.8160 mL 2.0401 mL
    DMSO 40 mM 0.0612 mL 0.3060 mL 0.6120 mL 1.5301 mL
    50 mM 0.0490 mL 0.2448 mL 0.4896 mL 1.2241 mL
    60 mM 0.0408 mL 0.2040 mL 0.4080 mL 1.0200 mL
    80 mM 0.0306 mL 0.1530 mL 0.3060 mL 0.7650 mL
    100 mM 0.0245 mL 0.1224 mL 0.2448 mL 0.6120 mL
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    NCT-503 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    NCT-5031916571-90-8NCT503NCT 503Phosphoglycerate Dehydrogenase (PHGDH)blood-brain barrierNAD+selenoprotein P3-phosphoglycerate dehydrogenasePHGDHglutathione peroxidase 1miceSELENOP3-phosphoglycerateGPX1Inhibitorinhibitorinhibit

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