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

PYZD-4409 

Cat. No.: HY-13297 Purity: >98.0%
Handling Instructions

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 (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 119 In-stock
Estimated Time of Arrival: December 31
5 mg USD 108 In-stock
Estimated Time of Arrival: December 31
10 mg USD 178 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Estimated Time of Arrival: December 31
100 mg USD 780 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 2 publication(s) in Google Scholar

Top Publications Citing Use of Products

Publications Citing Use of MCE PYZD-4409

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

    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].

    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].

    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.

    423148-78-1

    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 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 35 mg/mL (99.53 mM)

    *"≥" 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
    10 mM 0.2844 mL 1.4218 mL 2.8436 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    *All of the co-solvents are provided by MCE.
    References
    • 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.
    • Molarity Calculator

    • Dilution Calculator

    The molarity calculator equation

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

    Mass   Concentration   Volume   Molecular Weight *
    = × ×

    The dilution calculator equation

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
    × = ×
    C1   V1   C2   V2

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product name

     

    Salutation

    Applicant name *

     

    Email address *

    Phone number *

     

    Organization name *

    Country or Region *

     

    Requested quantity *

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    PYZD-4409
    Cat. No.:
    HY-13297
    Quantity: