2. Metabolic Enzyme/Protease
  3. E1/E2/E3 Enzyme
  4. PYZD-4409

PYZD-4409 is a specific inhibitor of the ubiquitin-activating enzyme UBA1 with an IC50 of 20 μM (cell-free enzymatic assay). PYZD-4409 induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells.

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

PYZD-4409 Chemical Structure

PYZD-4409 Chemical Structure

CAS No. : 423148-78-1

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 99 In-stock
Solution
10 mM * 1 mL in DMSO USD 99 In-stock
Solid
5 mg USD 90 In-stock
10 mg USD 150 In-stock
25 mg USD 280 In-stock
50 mg USD 450 In-stock
100 mg USD 650 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 2 publication(s) in Google Scholar

PYZD-4409 Related Antibodies

Top Publications Citing Use of Products

1 Publications Citing Use of MCE PYZD-4409

WB

    PYZD-4409 purchased from MedChemExpress. Usage Cited in: Mol Cell Biol. 2018 Jul 16;38(15). pii: e00024-18.  [Abstract]

    Western blotting assays demonstrate that treatment of 20 μM PYR-41 or 20 μM PYZD-4409 inhibits ubiquitination and CD133 secretion. Hsp90 and β-actin are used as loading controls.

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    PYZD-4409 is a specific inhibitor of the ubiquitin-activating enzyme UBA1 with an IC50 of 20 μM (cell-free enzymatic assay). PYZD-4409 induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells[1].

    IC50 & Target

    IC50: 20 μM (ubiquitin-activating enzyme UBA1)[1]
    In Vitro

    PYZD-4409 (10-40 μM; 72 hours; myeloma, leukemia, and solid tumor cell lines, primary AML cells and normal hematopoietic cells) induces cell death with a LD50 less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an LD50 of approximately 15 to 20 μM. PYZD-4409 is preferentially cytotoxic to malignant cells over normal hematopoietic cells[1].
    PYZD-4409 (50 μM; 4 hours; K562 leukemia cells) treatment blocks the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34[1].
    PYZD-4409 (0-25 μM; 24 hours; K562 leukemia cells) significantly increases both mRNA and protein levels of Grp78 and Hsp70. In addition, PYZD-4409 increases levels of phospho-JNK and phospho-p38 mitogen-activated protein kinase, which have also been linked to ER stress and the unfolded protein response[1].

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

    PYZD-4409 Related Antibodies

    Cell Cytotoxicity Assay[1]

    Cell Line: Myeloma, leukemia, and solid tumor cell lines, primary AML cells and normal hematopoietic cells
    Concentration: 10 μM, 20 μM, 30 μM, 40 μM
    Incubation Time: 72 hours
    Result: Induced cell death with a LD50 less than 10 μM in 5 of 8 leukemia and myeloma cell lines. In contrast, solid tumor cell lines were less sensitive with an LD50 of approximately 15 to 20 μM.

    Western Blot Analysis[1]

    Cell Line: K562 leukemia cells
    Concentration: 50 μM
    Incubation Time: 4 hours
    Result: Blocked the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc34.

    RT-PCR[1]

    Cell Line: K562 cells
    Concentration: 0 μM, 10 μM, 25 μM
    Incubation Time: 24 hours
    Result: Significantly increased both mRNA and protein levels of Grp78 and Hsp70.
    In Vivo

    PYZD-4409 (10 mg/kg; intraperitoneal injection; daily on alternate days; for 16 days; male severe combined immunodeficient mice) decreases tumor weight and volume without untoward toxicity[1].

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

    Animal Model: Male severe combined immunodeficient (SCID) mice with MDAY-D2 murine leukemia cells[1]
    Dosage: 10 mg/kg
    Administration: Intraperitoneal injection; daily on alternate days; for 16 days
    Result: Delayed tumor growth and decreased tumor weight without untoward toxicity.
    Molecular Weight

    351.67

    Formula

    C14H7ClFN3O5
    CAS No.
    Appearance

    Solid

    Color

    Light brown to black

    SMILES

    FC1=CC=C(N2C(/C(C(N2)=O)=C\C3=CC=C([N+]([O-])=O)O3)=O)C=C1Cl
    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 : ≥ 35 mg/mL (99.53 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.8436 mL 14.2179 mL 28.4357 mL
    5 mM 0.5687 mL 2.8436 mL 5.6872 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)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    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

    ×
    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: ≥ 2.5 mg/mL (7.11 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      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.
    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.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    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
    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
    DMSO 1 mM 2.8436 mL 14.2179 mL 28.4357 mL 71.0894 mL
    5 mM 0.5687 mL 2.8436 mL 5.6871 mL 14.2179 mL
    10 mM 0.2844 mL 1.4218 mL 2.8436 mL 7.1089 mL
    15 mM 0.1896 mL 0.9479 mL 1.8957 mL 4.7393 mL
    20 mM 0.1422 mL 0.7109 mL 1.4218 mL 3.5545 mL
    25 mM 0.1137 mL 0.5687 mL 1.1374 mL 2.8436 mL
    30 mM 0.0948 mL 0.4739 mL 0.9479 mL 2.3696 mL
    40 mM 0.0711 mL 0.3554 mL 0.7109 mL 1.7772 mL
    50 mM 0.0569 mL 0.2844 mL 0.5687 mL 1.4218 mL
    60 mM 0.0474 mL 0.2370 mL 0.4739 mL 1.1848 mL
    80 mM 0.0355 mL 0.1777 mL 0.3554 mL 0.8886 mL
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.

    PYZD-4409 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:

    PYZD-4409423148-78-1PYZD4409PYZD 4409E1/E2/E3 EnzymeE1 activating enzymeE2 conjugating enzymeE3 ligating enzymeUbiquitin activating enzymeUbiquitin conjugating enzymeUbiquitin ligaseInhibitorinhibitorinhibit

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Salutation

    Applicant Name *

    		 

    Email Address *

    Phone Number *

    		 

    Organization Name *

    Department *

    		 

    Requested quantity *

    Country or Region *

    		      

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    PYZD-4409
    Cat. No.:
    HY-13297
    Quantity:
    MCE Japan Authorized Agent:

    Customer Review

    Thank You for Your Feedback!

    Request for HNMR Report

    Please fill out this form to request the QC report. We will send it to your Email address shortly.

    Your information is safe with us. * Required Fields.

    Product Name

    		  

    Lot #

    Applicant Name *

    		 

    Email Address *

    Phone Number

    		 

    Department *

    Organization Name *

    		 

    Country or Region *

    Remarks

    SAFETY DATA SHEET (SDS)

    English - EN (420 KB) Français - FR (420 KB) Deutsch - DE (420 KB) Norwegian - NO (420 KB) Español - ES (420 KB) Swedish - SV (420 KB)

    Request for HNMR Report

    We have received your request and will respond to you as soon as possible.