My cart
In the shopping cart is not goods, to choose and buy!
  • Product Name
  • Size
  • Quantity
  • Amount
    Selected items : 0 pieces Total : CHECK OUT()
    Pretomanid (PA-824)
    Pretomanid (PA-824)

    Price:
    Market Price:

    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V0011
    CAS #: 187235-37-6 Purity ≥98%

    Description: Pretomanid (also known as PA-824; PA824), a bicyclic nitroimidazolepyran analog, is a novel, potent and selective anti-tuberculosis (TB) drug approved in 2019 for treating multi-drug-resistant tuberculosis with an MIC of less than 2.8 μM. It is generally used together with bedaquiline and linezolid. PA-824 has been found to exhibit bactericidal activity against replicating bacilli and non-replicating bacilli under hypoxic or prolonged culture conditions in a dose dependent fashion through two possible mechanisms, which include PA-824 induced inhibition of ketomycolate synthesis and PA-824 mediated donation of nitric oxide during enzymatic nitro-reduction. 

    References: Antimicrob Agents Chemother. 2005 Jun;49(6):2294-301; Antimicrob Agents Chemother. 2011 Dec;55(12):5718-22; Antimicrob Agents Chemother. 2011 Jan;55(1):239-45.  

    Customer Validation
    Top Publications Citing Invivochem Products
    • Citation of InvivoChem Vorinostat (V0255) by Nature 2021, 597(7874):119-125
    • Citation of InvivoChem Larotrectinib (V2599) by Cell. 2020 Nov 25;183(5):1202-1218.e25
    • Citation of InvivoChem Eprenetapopt (APR-246) by Science Adv 2022: 8, eabm9427.
    • Citation of InvivoChem 5-azacytidine (V0404) by Nature 2021, DOI: 10.1038/s41586-021-03850-3
    • Citation of InvivoChem Larotrectinib (V2599) by Cell 2020, doi: 10.1016/j.cell.2020.10.016.
    • Citation of InvivoChem Eprenetapopt (APR-246) by Science Adv 2022, doi: 10.1126/sciadv.abm9427.
    • Citation of InvivoChem Vorinostat/SAHA (V0255) by Nature 2021, DOI: 10.1038/s41586-021-03850-3.
    • Citation of InvivoChem Vitrakvi by Cell 2020, PMID: 33142117 PMCID: PMC8100789
    • Citation of InvivoChem APR-246 by Science Adv 2022, PMID: 36103522.
    • Citation of InvivoChem 5-azacytidine (V0404) by Nature 2021, DOI: 10.1038/s41586-021-03850-3.
    • Citation of InvivoChem LOXO-101 by Cell 2020, PMID: 33142117 PMCID: PMC8100789
    • Citation of InvivoChem Eprenetapopt by Science Adv 2022, PMID: 36103522.
    • Citation of InvivoChem Vorinostat/SAHA (V0255) by Nature 2021, PMID: 34433969
    • Citation of InvivoChem  ARRY-470 by Cell 2020, PMID: 33142117 PMCID: PMC8100789
    • Citation of InvivoChem 5-azacytidine (V0404) by Nature 2021, PMID: 34433969
    • Citation of InvivoChem BMH-21 (V1435) by Cell Stem Cell 2020, 26(6): 845-861.e12.
    • Citation of InvivoChem Eprenetapopt (APR-246) by Science Adv 2022, doi: 10.1126/sciadv.abm9427.
    • Citation of InvivoChem 5-azacytidine (V0404) by Nature 2021, DOI: 10.1038/s41586-021-03850-3.
    • Citation of InvivoChem V33339 Lys-SMCC-DM1 by PNAS Nexus 2022, pgac063, https://academic.oup.com/pna
    • Citation of InvivoChem 5-azacytidine by Nature 2021, PMID: 34433969
    • Citation of InvivoChem Ruxolitinib/Filgotinib/BMS-911543/Decernotinib by J Allergy Clin Immunol 2020
    • Citation of InvivoChem LGK974 /WNT974 (V1353) by  Cancer Cell 2021 Apr 12;39(4):529-547.e7.
    • Citation of InvivoChem V1386 Napabucasin (BBI-608) by J Exp Clin Cancer Res 2021 Oct 13;40(1):319.
    • Citation of InvivoChem 5-azacytidine (V0404) by Nature 2021, DOI: 10.1038/s41586-021-03850-3.
    • Citation of InvivoChem Epacadostat/INCB024360 (V0942) by Cancer Discov 2022: 12(4):1106-1127.
    • Citation of InvivoChem S63845 (V2797) by Cell Death and Disease 2020, 11:316.
    • Citation of InvivoChem BMS-582949 (V2668) by Cells 2020, 9(6):1472.
    • Citation of InvivoChem Apiin (V4467) by J Med Chem 2020, 63(15):8338-8358.
    • Citation of InvivoChem V0001 venetoclax by WO2021231323A1
    Publications Citing InvivoChem Products
    • Physicochemical and Storage Information
    • Protocol
    • Quality Control Documentation
    • Related Biological Data
    • Customer Review
    Molecular Weight (MW)359.26 
    FormulaC14H12F3N3O5 
    CAS No.187235-37-6 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 72 mg/mL (200.4 mM) 
    Water: <1 mg/mL
    Ethanol: 16 mg/mL (44.5 mM)
    Solubility (In vivo)0.5% methylcellulose: 30 mg/mL 
    SynonymsPA-824; Pretomanid; PA 824; PA824; 


    • 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
    In Vitro

    In vitro activity: In vitro, PA-824 exhibits the high activity against multidrug-resistant clinical isolates from Asia (India and South Korea) and from throughout the United States (MIC < 1 μg/ml) and is equally active against the drug-sensitive and multidrug-resistant isolates of M. tuberculosis (MICs range, 0.039 to 0.531 μg/ml). A recent study shows that single-nucleotide polymorphisms of PA-824 resistance genes (fgd1 [Rv0407] and ddn [Rv3547]) don't significantly affect the PA-824 MICs (≤ 0.25 μg/ml).


    Kinase Assay: Pretomanid (PA-824) is a small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis; the MIC values of PA-824 against a panel of MTB pan-sensitive and rifampin mono-resistant clinical isolates ranged from 0.015 to 0.25 ug/ml. IC50 value: 0.015 to 0.25 ug/ml (MICs).


    Cell Assay: A method is used to determine the MICs by a microdilution plate assay by using M. tuberculosis H37Rv. INH is dissolved in sterile, double-distilled water at a stock concentration of 500 μg/ml. PA-824 is dissolved in 100% dimethyl sulfoxide (DMSO) to a stock concentration of 100 μg/ml. A 1:2 dilution series of both compounds is made in a separate 96-well microtiter plate by using the same diluents. The interior 60 wells of a 96-well round-bottom microtiter assay plate are seeded with 98 μl of bacterial suspension. Two microliters of each drug is transferred to the assay plate wells containing bacteria. The final concentrations of INH in the wells range from 10.0 to 0.039 μg/mL; the final concentrations of PA-824 range from 2.0 μg/mL to 8.0 pg/mL. The assay plates are incubated at 37 °C for at least 21 days and are observed every 3 to 4 days to evaluate changes in growth. Inhibition of growth is determined both by visual examination and with a spectrophotometer at an OD600.

    In VivoIn the rapid tuberculosis mouse model, PA-824 shows significant anti-microbial activity in a dose-dependent manner: at 50 mg/kg, PA-824 in MC produces a more than 1-log reduction of the CFU in the lungs; at 100 mg/kg it produces about a 2-log reduction, and at 300 mg/kg it produces a 3-log reduction. Furthermore, long-term treatment of PA-824 at 100 mg/kg in cyclodextrin/lecithin also leads to the reduction of the bacterial load below 500 CFU in the lungs and spleen. PA-824 exhibits time-dependent anti-microbial activity in a murine model of tuberculosis with a maximal observed bactericidal effect of 0.1 log CFU/day over 24 days. 
    Animal modelGamma interferon gene-disrupted (GKO) mice are infected via a low-dose aerosol exposure to M. tuberculosis Erdman.  
    Formulation & DosageFormulated either in 0.5% methylcellulose (MC) or in cyclodextrin/lecithin (CM2); ≤300 mg/kg; p.o. 
    ReferencesAntimicrob Agents Chemother. 2005 Jun;49(6):2294-301; Antimicrob Agents Chemother. 2011 Dec;55(12):5718-22; Antimicrob Agents Chemother. 2011 Jan;55(1):239-45.  


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    评论

      Home Prev Next Last page / pices

      发评论

      ×
      Your information is safe with us. * Required Fields.
      Products are for research use only;  We do not sell to patients
      Tel: 1-708-310-1919
      Fax: 1-708-557-7486
      Subscribe to our E-newsletter
      • Name*
      • *
      • E-mail*
      • *
      • instructions:
      • *
      Copyright 2020 InvivoChem LLC | All Rights Reserved
      prompt
      Do you confirm the receipt?