2. Autophagy Neuronal Signaling Metabolic Enzyme/Protease Apoptosis Membrane Transporter/Ion Channel Immunology/Inflammation NF-κB
  3. PINK1/Parkin Glutathione Peroxidase Sodium Channel ATP Synthase NOD-like Receptor (NLR) Mitophagy Ferroptosis Autophagy Apoptosis Reactive Oxygen Species (ROS)
  4. Dexpramipexole

Dexpramipexole  (Synonyms: (R)-Pramipexole; R-(+)-Pramipexole; KNS-760704)

Cat. No.: HY-17355B Purity: 99.56%
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Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Nav1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

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

CAS No. : 104632-28-2

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Based on 2 publication(s) in Google Scholar

Other Forms of Dexpramipexole:

Dexpramipexole Related Antibodies

Top Publications Citing Use of Products

    Dexpramipexole purchased from MedChemExpress. Usage Cited in: Neuroreport. 2023 Mar 1;34(4):220-231.  [Abstract]

    Dexpramipexole (DPX; 3 mg/kg; i.p.; once daily for 6 consecutive days) attenuates the LPS-induced increase in the number of TUNEL-positive cells in the hippocampus in SAE mice.

    Dexpramipexole purchased from MedChemExpress. Usage Cited in: Neuroreport. 2023 Mar 1;34(4):220-231.  [Abstract]

    Dexpramipexole (DPX; 3 mg/kg; i.p.; once daily for 6 consecutive days) attenuates LPS-induced activation of microglia and astrocytes in the hippocampus in SAE mice. (a) Representative images of Iba-1 staining and quantification of Iba-1 (green) fluorescence intensity in the hippocampal CA1 and DG regions. (b) Representative images of GFAP staining and quantification of GFAP (red) fluorescence intensity in the hippocampal CA1 and DG regions. DAPI staining is shown in blue.

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    GPX1 GPX4

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    Nav1.1 Nav1.2 Nav1.3 Nav1.4 Nav1.5 Nav1.6 Nav1.7 Nav1.8 Nav1.9

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    NLRP3 NLRP1 NOD1 NOD2

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Nav1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more[1][2][3][4][5][6].

    IC50 & Target[5][1]

    Nav1.8

     

    GPX4

     

    PINK1

     

    NLRP3 inflammasome

     

    In Vitro

    Dexpramipexole (5-200 μM; 24 h) shows no cytotoxicity to primary cardiomyocytes isolated from neonatal rats at concentrations below 100 μM, while the compound at 200 μM reduces cell viability[1].
    Dexpramipexole (2-50 μM) protects primary neonatal rat cardiomyocytes against hypoxia/reoxygenation (H/R)-induced injury by enhancing cell viability and reducing LDH release[1].
    Dexpramipexole (2-50 μM) upregulates the expression level of PINK1 protein in primary cardiomyocytes from neonatal rats treated with H/R[1].
    Dexpramipexole protects primary cardiomyocytes from neonatal rats against H/R-induced mitochondrial dysfunction by reducing mPTP opening, decreasing ROS production and restoring mitochondrial membrane potential[1].
    Dexpramipexole enhances ATG7-dependent mitophagy in primary neonatal rat cardiomyocytes subjected to H/R, which is characterized by increased formation of mitophagosomes, enhanced autophagic mitochondrial sequestration, and improved mitochondrial clearance[1].
    Dexpramipexole activates PINK1 and Parkin and promotes mitochondrial fission in primary neonatal rat cardiomyocytes exposed to H/R[1].
    Dexpramipexole protects primary cardiomyocytes from neonatal rats against H/R injury by upregulating PINK1- and Parkin-dependent mitophagy[1].
    Dexpramipexole (10 μM; 5 min) inhibits tetrodotoxin-resistant sodium currents in primary cultured rat dorsal root ganglion neurons with an IC50 of 294.4 nM, and does not alter the voltage-dependent activation or inactivation properties of the channels[5].
    Dexpramipexole (10 μM) selectively inhibits Nav1.8-mediated sodium currents in primary cultured dorsal root ganglion neurons from wild-type mice[5].

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

    Dexpramipexole Related Antibodies
    In Vivo

    Dexpramipexole (1 mg/kg; single administration) alleviates myocardial ischemia/reperfusion injury in male C57BL/6 mice by reducing infarct size, restoring cardiac function, decreasing serum levels of myocardial injury biomarkers, and enhancing PINK1/Parkin-dependent mitophagy[1].
    Dexpramipexole (5-20 mg/kg; i.p., once daily for 14 consecutive days) improves survival rate, body weight gain, spontaneous activity, motor coordination and forelimb muscle strength, reduces hematoma volume, alleviates white matter injury, decreases iron and ROS accumulation, and inhibits ferroptosis by upregulating GPX4 and FSP1 in mice with intracerebral hemorrhage[2].
    Dexpramipexole (3 mg/kg; i.p.; once daily for 6 consecutive days) improves lipopolysaccharide (LPS)-induced cognitive impairment in sepsis-associated encephalopathy (SAE), preserves the morphology and function of hippocampal mitochondria in mice, and inhibits mitochondria-mediated pyroptosis and apoptosis[3].
    Dexpramipexole (3-20 mg/kg; 20-140 μg/20 μL; p.o.; i.p.; hind paw s.c.; single administration) exerts effective analgesic effects in various mouse models of nociceptive pain (e.g., inflammatory pain, visceral pain) and neuropathic pain (e.g., chemotherapy-induced pain, nerve compression pain, diabetic neuropathic pain)[5].

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

    Animal Model: C57BL/6 (male, 9-10 weeks old, 24-26 g; intracerebral hemorrhage induced by stereotactic injection of autologous tail vein blood)[2]
    Dosage: 5 mg/kg; 10 mg/kg; 20 mg/kg
    Administration: i.p., once daily for 14 days
    Result: Significantly increased the survival rate of mice after cerebral hemorrhage.
    Slowed down the postoperative weight loss and promoted the recovery of motor function, motor coordination ability, muscle strength and comprehensive neurological function (BMS).
    Reduced iron deposition around the hematoma and the accumulation of reactive oxygen species.
    Increased the expression of GPX4 and FSP1.
    Animal Model: C57BL/6 (male, 3 months old, 20-28 g, LPS-induced sepsis-associated encephalopathy)[3]
    Dosage: 3 mg/kg
    Administration: i.p.; daily; 6 consecutive days
    Result: Improved the long-term cognitive dysfunction caused by LPS, particularly spatial working memory and hippocampus-dependent memory.
    Protected the mitochondria of hippocampal neurons, improved their morphology (reduced swelling) and function (maintained ATP levels, reduced ROS).
    Inhibited pyroptosis and apoptosis of cells
    Animal Model: CD-1 (male, 20-25 g, intraplantar formalin injection-induced inflammatory pain)[5]
    Dosage: 3 mg/kg; 10 mg/kg; 20 μg/20 μL; 70 μg/20 μL; 140 μg/20 μL
    Administration: p.o.; single dose 1 h before test; i.p.; single dose 1 h before test; s.c. in hind paw; single dose 10 min before test
    Result: Reduced time spent in pain-like behaviors during the early formalin phase (10 mg/kg p.o.).
    Reduced time spent in pain-like behaviors dose-dependently during the late formalin phase (3 mg/kg, 10 mg/kg p.o.).
    Reduced time spent in pain-like behaviors dose-dependently during the late formalin phase (3 mg/kg, 10 mg/kg i.p.).
    Reduced time spent in pain-like behaviors during the late formalin phase (70 μg/20 μL, 140 μg/20 μL s.c.).
    Caused no effect on pain-like behaviors in the early phase at any tested subdermal dose.
    Animal Model: CD-1 (male, 20-25 g; female, intraperitoneal acetic acid injection-induced visceral pain)[5]
    Dosage: 10 mg/kg; 20 mg/kg
    Administration: i.p.; single dose 1 h before test
    Result: Reduced the number of abdominal writhings dose-dependently in male mice
    . Reduced the number of abdominal writhings in female mice.
    Animal Model: CD-1 (male, 20-25 g, ankle complete Freund adjuvant injection-induced chronic inflammatory arthritis pain)[5]
    Dosage: 70 μg/20 μL
    Administration: s.c. in hind paw; single dose 10 min before each test on day 7, 14, 21
    Result: Increased mechanical thresholds at day 7, 14, and 21 post CFA injection.
    Animal Model: CD-1 (subcutaneous oxaliplatin injection-induced acute chemotherapy-induced neuropathic pain)[5]
    Dosage: 10 mg/kg; 70 μg/20 μL
    Administration: i.p.; single dose 30 min post oxaliplatin; s.c. in hind paw; single dose 50 min post oxaliplatin
    Result: Reduced cold pain-related behaviors at 1, 2, 3, 4, and 5 h post oxaliplatin injection (10 mg/kg i.p.).
    Reduced cold pain-related behaviors at 1 hour post oxaliplatin injection (70 μg/20 μL, s.c.).
    Animal Model: CD-1 (intraperitoneal oxaliplatin injection-induced chronic chemotherapy-induced neuropathic pain)[5]
    Dosage: 10 mg/kg
    Administration: i.p.; single dose 1 h before test; p.o.; single dose 1 h before test
    Result: Reduced cold allodynia at day 21 post initial oxaliplatin injection (10 mg/kg i.p.).
    Reduced cold allodynia at 1, 3, and 6 hours post dosing, with effects diminishing by 9 hours (10 mg/kg p.o.).
    Animal Model: CD-1 (male, 20-25 g, chronic constriction injury of right sciatic nerve-induced neuropathic pain)[5]
    Dosage: 10 mg/kg
    Administration: i.p.; single dose 1 h before test
    Result: Reduced mechanical allodynia in the injured hind paw.
    Animal Model: CD-1 (intraperitoneal streptozotocin injection-induced diabetic neuropathic pain, blood glucose > 250 mg/dl confirmed 3 weeks post-injection)[5]
    Dosage: 10 mg/kg
    Administration: i.p.; single dose 1 h before test
    Result: Increased latency to pain-related behaviors in diabetic mice.
    Molecular Weight

    211.33

    Formula

    C10H17N3S
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    NC1=NC(CC[C@@H](NCCC)C2)=C2S1
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 10 mg/mL (47.32 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 4.7319 mL 23.6597 mL 47.3194 mL
    5 mM 0.9464 mL 4.7319 mL 9.4639 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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    This equation is commonly abbreviated as: C1V1 = C2V2

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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: ≥ 1 mg/mL (4.73 mM); Clear solution

      This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 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% (20% SBE-β-CD in Saline)

      Solubility: ≥ 1 mg/mL (4.73 mM); Clear solution

      This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 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:

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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: 99.56%

    SDS (396 KB)

    COA (243 KB) HNMR (415 KB) LCMS (94 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. 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
    DMSO 1 mM 4.7319 mL 23.6597 mL 47.3194 mL 118.2984 mL
    5 mM 0.9464 mL 4.7319 mL 9.4639 mL 23.6597 mL
    10 mM 0.4732 mL 2.3660 mL 4.7319 mL 11.8298 mL
    15 mM 0.3155 mL 1.5773 mL 3.1546 mL 7.8866 mL
    20 mM 0.2366 mL 1.1830 mL 2.3660 mL 5.9149 mL
    25 mM 0.1893 mL 0.9464 mL 1.8928 mL 4.7319 mL
    30 mM 0.1577 mL 0.7887 mL 1.5773 mL 3.9433 mL
    40 mM 0.1183 mL 0.5915 mL 1.1830 mL 2.9575 mL
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    Dexpramipexole 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:

    Dexpramipexole104632-28-2(R)-Pramipexole R-(+)-Pramipexole KNS-760704KNS760704KNS 760704KNS-760704PINK1/ParkinGlutathione PeroxidaseSodium ChannelATP SynthaseNOD-like Receptor (NLR)MitophagyFerroptosisAutophagyApoptosisReactive Oxygen Species (ROS)PTEN-induced kinase 1/ParkinNa channelsNa+ channelsMitochondrial AutophagyParkinPINK1Na?1.8 sodium channelsneonatal rat primary cardiomyocytesFSP1F1/F0 ATP synthase b-subunitsoligomycin sensitivity-conferring proteinNLRP3 inflammasomeGPX4dorsal root ganglion neuronsInhibitorinhibitorinhibit

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