2. Membrane Transporter/Ion Channel Neuronal Signaling Metabolic Enzyme/Protease
  3. Calcium Channel Cytochrome P450
  4. NNC 55-0396

NNC 55-0396  (Synonyms: NNC 55-0396 dihydrochloride)

Cat. No.: HY-50722 Purity: 98.43%
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NNC 55-0396 (NNC 55-0396 dihydrochloride) is a blood-brain-barrier-permeable T-type Ca2+ channel inhibitor and pan-P450 inhibitor. NNC 55-0396 selectively inhibits T-type Ca2+ channels, suppresses HIF-1α expression and stability and inhibits Kv currents. NNC 55-0396 reduces brain infarct and attenuates neurological dysfunction. NNC 55-0396 inhibits the activity of multiple P450 enzymes. NNC 55-0396 (free base) can be used for the research of brain injury, hypertension, and glioblastoma.

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

CAS No. : 357400-13-6

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10 mM * 1 mL in DMSO
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Customer Review

Based on 5 publication(s) in Google Scholar

Other Forms of NNC 55-0396:

NNC 55-0396 Related Antibodies

Top Publications Citing Use of Products

    NNC 55-0396 purchased from MedChemExpress. Usage Cited in: Br J Pharmacol. 2021 Oct;178(20):4155-4175.  [Abstract]

    Effect of NaHS on neuronal viability against OGD/R injury in vitro. Cell viability was measured by CCK-8 at 24 h post-reoxygenation. Data: mean ± SD, n=6. #P<0.05 vs Normal; *P<0.05 vs Model (OGD/R); &P<0.05 vs NaHS (1 µM); $P<0.05 vs BMS-191011 (BMS) (10 µM); %P<0.05 vs NaHS+Verapamil (Ver) (100 µM); ※P<0.05 vs Verapamil alone. NNC 55-0396 (NNC): 100 µM.

    NNC 55-0396 purchased from MedChemExpress. Usage Cited in: Br J Pharmacol. 2021 Oct;178(20):4155-4175.  [Abstract]

    Effect of NaHS on neuronal viability against OGD/R injury in vitro. Cell viability was measured by CCK-8 at 24 h post-reoxygenation. Data: mean ± SD, n=6. #P<0.05 vs Normal; *P<0.05 vs Model (OGD/R); &P<0.05 vs NaHS (1 µM); $P<0.05 vs BMS-191011 (BMS) (10 µM); %P<0.05 vs NaHS+Verapamil (Ver) (100 µM); ※P<0.05 vs Verapamil alone. NNC 55-0396 (NNC): 100 µM.

    View All Calcium Channel Isoform Specific Products:

    View All Isoforms
    N-type calcium channel L-type calcium channel P/Q-type calcium channel T-type calcium channel Calcium Channel

    View All Cytochrome P450 Isoform Specific Products:

    View All Isoforms
    CYP1 CYP2 CYP3 CYP4 CYP11 CYP17 Aromatase/CYP19A1 CYP26 CYP51 CYP1A2 CYP2D6 CYP2C9 CYP2C19 CYP3A CYP3A4 CYP17A1

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    NNC 55-0396 (NNC 55-0396 dihydrochloride) is a blood-brain-barrier-permeable T-type Ca2+ channel inhibitor and pan-P450 inhibitor. NNC 55-0396 selectively inhibits T-type Ca2+ channels, suppresses HIF-1α expression and stability and inhibits Kv currents. NNC 55-0396 reduces brain infarct and attenuates neurological dysfunction. NNC 55-0396 inhibits the activity of multiple P450 enzymes. NNC 55-0396 (free base) can be used for the research of brain injury, hypertension, and glioblastoma[1][2][3][4][5].

    IC50 & Target[2][3]

    CYP3A4

    300 nM (IC50)

    CYP3A4

    210 nM (Ki)

    CYP2D6

    29 nM (IC50)

    CYP2D6

    2.8 nM (Ki)

    T-type calcium channel

     

    In Vitro

    NNC 55-0396 potently inhibits recombinant human CYP3A4 and CYP2D6 at 100 nM and 10 μM, with weaker or no inhibition of recombinant human CYP1A2, CYP2E1, CYP2C9, CYP2C19, and CYP2C8 at these concentrations[2].
    NNC 55-0396 inhibits recombinant human CYP3A4 BFC debenzylation activity with an IC50 of 300 nM and a Ki of 210 nM[2].
    NNC 55-0396 inhibits recombinant human CYP2D6 AMMC N-demethylation activity with an IC50 of 29 nM and a Ki of 2.8 nM[2].
    NNC 55-0396 inhibits CYP3A4-mediated testosterone 6β-hydroxylase activity in human liver microsomes with an IC50 of 11.0 μM and a Ki of 3.9 μM[2].
    NNC 55-0396 inhibits CYP2D6-mediated harmaline metabolism in human liver microsomes with an IC50 of 72.6 nM and a Ki of 57.1 nM[2].
    NNC 55-0396 (1-20 μM; 72 h) inhibits the growth of HepG2 cells more potently in galactose medium than glucose medium[3].
    NNC 55-0396 (1-5 μM; 5 h) dose-dependently inhibits hypoxia-induced HIF-1α protein stability in HepG2 cells, with a near-complete reduction at 5 μM after 4 h hypoxic incubation, without affecting HIF-1β levels[3].
    NNC 55-0396 (1-5 μM; 5 h) dose-dependently increases the hydroxylation of HIF-1α in HepG2 cells under hypoxic conditions, with a 6-fold increase observed at 5 μM after 4 h incubation[3].
    NNC 55-0396 (1-5 μM; 5 h) reduces hypoxia-induced mitochondrial ROS levels in HepG2 cells[3].
    NNC 55-0396 (1 μM) decreases the half-life of hypoxia-stabilized HIF-1α in HepG2 cells, reducing it from over 80 minutes to less than 70 minutes[3].
    NNC 55-0396 (1-5 μM; 5 h) inhibits Desferrioxamine-induced HIF-1α stabilization in HepG2 cells, with a 50% reduction observed at 5 μM after 4 h incubation[3].
    NNC 55-0396 (1-5 μM; 75 min) reduces hypoxia-induced HIF-1α protein levels in HepG2 cells, with significant suppression observed at 1 μM and 5 μM[3].
    NNC 55-0396 (1-5 μM; 75 min) inhibits hypoxia-induced phosphorylation of mTOR and p70S6K in HepG2 cells, with a 70% reduction in phospho-mTOR levels observed at 5 μM after 15 min hypoxic incubation[3].
    NNC 55-0396 (1-5 μM; 17 h) dose-dependently reduces hypoxia-induced VEGF expression in HepG2 cells, with significant suppression observed at 1 μM and 5 μM after 16 h hypoxic incubation[3].
    NNC 55-0396 (0.001-10 mM; 1 min) dose-dependently inhibits Kv currents in freshly isolated rabbit coronary arterial smooth muscle cells with an IC50 of 0.08 mM[4].
    NNC 55-0396 potently blocks recombinant Cav3.1 T-type calcium channels in HEK293 cells with an IC50 of 6.8 μM, via a state-dependent[5].

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

    NNC 55-0396 Related Antibodies

    Cell Viability Assay[3]

    Cell Line: human liver carcinoma HepG2 cells
    Concentration: 1 μM; 2 μM; 5 μM; 7 μM; 10 μM; 20 μM
    Incubation Time: 72 h
    Result: Exhibited stronger inhibitory effects on cell growth in galactose medium than in glucose medium.
    Increased glucose/galactose cell growth ratios significantly at concentrations of 5, 7, 10, and 20 μM.

    Western Blot Analysis[3]

    Cell Line: human liver carcinoma HepG2 cells
    Concentration: 1 μM; 5 μM
    Incubation Time: 5 h
    Result: Suppressed hypoxia-induced HIF-1α protein stability in a dose-dependent manner, with no effect on HIF-1β stability.
    Reduced HIF-1α expression to ~80% of hypoxic control levels at 1 μM.
    Reduced HIF-1α expression to ~20% of hypoxic control levels at 5 μM (p<0.001).\nIncreased the ratio of hydroxy-HIF-1α to total HIF-1α in a dose-dependent manner.
    Increased the ratio to ~250% of control levels at 1 μM.
    Increased the ratio to ~600% of control levels at 5 μM (p<0.001).

    Western Blot Analysis[3]

    Cell Line: human liver carcinoma HepG2 cells
    Concentration: 1 μM; 5 μM
    Incubation Time: 5 h
    Result: Inhibited DFO-induced HIF-1α stabilization.
    Reduced HIF-1α expression to ~100% of DFO-treated control levels at 1 μM.
    Reduced HIF-1α expression to ~50% of DFO-treated control levels at 5 μM (p<0.01).

    Western Blot Analysis[3]

    Cell Line: human liver carcinoma HepG2 cells
    Concentration: 1 μM; 5 μM
    Incubation Time: 75 min
    Result: Repressed hypoxia-induced phosphorylation of mTOR and p70S6K.
    Reduced phospho-mTOR levels to 0.8-fold of hypoxic control levels at 1 μM.
    Reduced phospho-mTOR levels to 0.3-fold of hypoxic control levels at 5 μM.
    Reduced phospho-p70S6K levels to 0.9-fold and 0.8-fold of hypoxic control levels at 1 μM and 5 μM, respectively.

    ELISA Assay[3]

    Cell Line: human liver carcinoma HepG2 cells
    Concentration: 1 μM; 5 μM
    Incubation Time: 17 h
    Result: Decreased hypoxia-induced VEGF expression in a dose-dependent manner.
    Reduced relative VEGF expression to ~220% of normoxic control levels at 1 μM (vs ~280% for hypoxic control; p<0.01).
    Reduced relative VEGF expression to ~180% of normoxic control levels at 5 μM (p<0.01).
    In Vivo

    NNC 55-0396 (5-20 mg/kg; i.p.; 2 doses) significantly reduces MCAO/R-induced ischemic brain injury and associated neurological dysfunctions[1].
    NNC 55-0396 (10-20 mg/kg; i.p.; every 2 days for 20 days) significantly reduces glioblastoma tumor weight by 40-60% and suppresses tumor angiogenesis via reduced HIF-1α, VEGF, and PECAM-1 expression in a subcutaneous mouse xenograft model[3].

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

    Animal Model: ddY mice (male, 3 weeks old, acclimated for a few weeks before experiments)[1]
    Dosage: 5 mg/kg; 20 mg/kg
    Administration: i.p.; 2 doses
    Result: Reduced MCAO/R-induced infarct area (at all measured distances from bregma) and infarct volume to ~30 mm3 (5 mg/kg i.p. pre-occlusion) and ~45 mm3 vs. vehicle ~70 mm3.
    Tended to attenuate some neurological dysfunctions, including increased test latency in the passive avoidance test and reduced time spent in right-biased bending.
    Animal Model: BALB/c-nu/nu (athymic nude) (4-week-old female, subcutaneous glioblastoma xenograft model)[3]
    Dosage: 10 mg/kg; 20 mg/kg
    Administration: i.p.; every 2 days for 20 days
    Result: Reduced xenograft tumor volume and weight relative to vehicle controls.
    Significantly reduced tumor weight (p<0.01 for 10 mg/kg, p<0.001 for 20 mg/kg).
    Significantly reduced HIF-1α, VEGF, and PECAM-1 expression levels in tumor tissue.
    Significantly decreased microvessel density (p<0.001 for 10 mg/kg, p<0.01 for 20 mg/kg).
    Caused no weight loss or liver toxicity in treated mice.
    Molecular Weight

    564.56

    Formula

    C30H40Cl2FN3O2
    CAS No.
    Appearance

    Solid

    Color

    Off-white to yellow

    SMILES

    O=C(C1CC1)O[C@@]2(CCN(CCCC3=NC4=CC=CC=C4N3)C)[C@@H](C(C)C)C5=C(C=C(F)C=C5)CC2.[H]Cl.[H]Cl
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    -20°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (177.13 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : ≥ 50 mg/mL (88.56 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7713 mL 8.8565 mL 17.7129 mL
    5 mM 0.3543 mL 1.7713 mL 3.5426 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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

    • Molarity Calculator

    • Dilution Calculator

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

    Mass
    =
    Concentration
    ×
    Volume
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    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

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    Volume (final)

    V2

    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: ≥ 2.08 mg/mL (3.68 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.08 mg/mL (3.68 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Calculation results:
    Working solution concentration: mg/mL
    This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
    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).
    Purity & Documentation

    Purity: 98.43%

    SDS (252 KB)

    COA (249 KB) HNMR (291 KB) LCMS (89 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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    H2O / DMSO 1 mM 1.7713 mL 8.8565 mL 17.7129 mL 44.2823 mL
    5 mM 0.3543 mL 1.7713 mL 3.5426 mL 8.8565 mL
    10 mM 0.1771 mL 0.8856 mL 1.7713 mL 4.4282 mL
    15 mM 0.1181 mL 0.5904 mL 1.1809 mL 2.9522 mL
    20 mM 0.0886 mL 0.4428 mL 0.8856 mL 2.2141 mL
    25 mM 0.0709 mL 0.3543 mL 0.7085 mL 1.7713 mL
    30 mM 0.0590 mL 0.2952 mL 0.5904 mL 1.4761 mL
    40 mM 0.0443 mL 0.2214 mL 0.4428 mL 1.1071 mL
    50 mM 0.0354 mL 0.1771 mL 0.3543 mL 0.8856 mL
    60 mM 0.0295 mL 0.1476 mL 0.2952 mL 0.7380 mL
    80 mM 0.0221 mL 0.1107 mL 0.2214 mL 0.5535 mL
    DMSO 100 mM 0.0177 mL 0.0886 mL 0.1771 mL 0.4428 mL

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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    NNC 55-0396 Related Classifications

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    • 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:

    NNC 55-0396357400-13-6Calcium ChannelCytochrome P450Ca2+ channelsCa channelsCYPsCYP3A4HIF-1αglioblastomamiddle cerebral artery occlusion and reperfusionHepG2 cellsHUVECHEK293 cellsT-type Ca2+ channelsKv currentsCYP2D6Inhibitorinhibitorinhibit

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