Pretomanid (PA-824)

Catalog No.S1162

For research use only.

PA-824 is an anti-tuberculosis drug for tuberculosis with MIC less than 2.8 μM.Phase 2.

Pretomanid (PA-824) Chemical Structure

CAS No. 187235-37-6

Purity & Quality Control

Choose Selective Bacterial Inhibitors

Biological Activity

Description PA-824 is an anti-tuberculosis drug for tuberculosis with MIC less than 2.8 μM.Phase 2.
Features An experimental anti-tuberculosis drug.
Targets
tuberculosis [1]
In vitro

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). [1] 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). [2]

In vivo In 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. [1] 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. [3]

Protocol (from reference)

Cell Research:[1]
  • Cell lines: M. tuberculosis H37Rv
  • Concentrations: 2.0 μg/mL - 8.0 pg/mL
  • Incubation Time: 21 days
  • Method: 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.
Animal Research:[1]
  • Animal Models: Gamma interferon gene-disrupted (GKO) mice are infected via a low-dose aerosol exposure to M. tuberculosis Erdman.
  • Dosages: ≤300 mg/kg
  • Administration: Administered via p. o.

Solubility (25°C)

In vitro

DMSO 72 mg/mL
(200.41 mM)
Water Insoluble
Ethanol ''16 mg/mL

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 359.26
Formula

C14H12F3N3O5

CAS No. 187235-37-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1C(COC2=NC(=CN21)[N+](=O)[O-])OCC3=CC=C(C=C3)OC(F)(F)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02333799 Completed Drug: Bedaquiline|Drug: PA-824|Drug: Linezolid Pulmonary Tuberculosis Global Alliance for TB Drug Development March 2015 Phase 3
NCT01674218 Completed Drug: Moxifloxacin|Drug: PA-824|Other: Placebo Tuberculosis National Institute of Allergy and Infectious Diseases (NIAID) September 2012 Phase 1
NCT01768273 Completed Drug: Midazolam|Drug: PA-824 Tuberculosis Global Alliance for TB Drug Development December 2009 Phase 1
NCT03202693 Completed Drug: PA-824 Tuberculosis Global Alliance for TB Drug Development March 2006 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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