What Is PA-824 and What Is Its Chemical Identity?

PA-824, generically known as Pretomanid, is a synthetic bicyclic nitroimidazo-oxazine compound developed for the treatment of tuberculosis (TB). It belongs to the nitroimidazole class of antibacterials, which are characterised by a nitro group that undergoes reductive activation inside susceptible mycobacterial cells.

The compound was developed under the auspices of the TB Alliance (Global Alliance for TB Drug Development) and received FDA approval in August 2019 for use in combination with bedaquiline and linezolid (the BPaL regimen) for pulmonary extensively drug-resistant TB (XDR-TB) and treatment-intolerant or non-responsive multidrug-resistant TB (MDR-TB).

For research procurement, PA-824 is available from Aladdin Scientific under SKU P129923. Researchers should consult the product specification sheet for purity, solubility, and storage conditions prior to use.

Mechanism of Action: How Does PA-824 Kill Mycobacteria?

PA-824 is a prodrug that requires intracellular bioactivation by the mycobacterial enzyme Ddn (deazaflavin-dependent nitroreductase, encoded by the Rv3547 gene in M. tuberculosis). This reductive activation, which uses the cofactor F420H2, converts the nitro group of PA-824 into reactive intermediates.

Under aerobic conditions (replicating bacteria), the activated species inhibit the biosynthesis of mycolic acids — essential long-chain fatty acids that are critical components of the mycobacterial cell wall. This disruption compromises cell wall integrity and leads to bacterial death.

Under anaerobic conditions (non-replicating, dormant bacteria), bioactivation generates reactive nitrogen species (including nitric oxide) that cause respiratory poisoning, effectively killing bacteria that are otherwise tolerant to many conventional antibiotics. This dual mechanism makes PA-824 particularly attractive for targeting both active TB disease and latent TB reservoirs in preclinical research models.

Research Applications of PA-824

PA-824 is widely used as a tool compound in TB drug discovery and antimycobacterial research. Key research applications include:

• In vitro antimycobacterial assays: Determining minimum inhibitory concentrations (MICs) against drug-sensitive and drug-resistant M. tuberculosis strains, as well as non-tuberculous mycobacteria.
• Mechanistic studies: Investigating the F420 biosynthesis and Ddn-dependent nitroreductase pathway, which is essential for understanding resistance mechanisms and identifying new drug targets.
• Combination regimen research: Evaluating synergistic or additive effects when PA-824 is combined with other antitubercular agents such as bedaquiline, linezolid, moxifloxacin, or pyrazinamide in checkerboard assays or mouse infection models.
• Resistance mechanism studies: Characterising mutations in fbiA, fbiB, fbiC, fgd1, and ddn genes that confer resistance to PA-824, informing clinical resistance surveillance.
• In vivo infection models: Testing efficacy in murine TB infection models under acute, chronic, or relapse-prevention protocols.

Researchers should note that PA-824 is intended for research use only and must be handled in accordance with applicable biosafety and institutional guidelines when used with live mycobacteria.

Handling, Solubility and Storage of PA-824

Proper handling and storage of PA-824 are essential to maintain compound integrity and ensure reproducible experimental results. The following are general guidance points; always refer to the Aladdin Scientific product datasheet (SKU P129923) for batch-specific specifications:

• Solubility: PA-824 has limited aqueous solubility. It is typically soluble in dimethyl sulfoxide (DMSO) and other organic solvents. When preparing working solutions for cell-based assays, ensure that the final DMSO concentration does not exceed levels that may affect cell viability (commonly ≤0.1% v/v).
• Storage: Store as a dry solid at the temperature specified on the datasheet (typically −20 °C or below, protected from light and moisture) to prevent degradation of the nitroimidazole moiety.
• Reconstitution: Prepare stock solutions in DMSO, aliquot to avoid repeated freeze-thaw cycles, and store aliquots at −20 °C.
• Safety: Handle in accordance with the Safety Data Sheet (SDS). Use appropriate personal protective equipment. The compound is for research use only and is not approved for human or veterinary use outside of its approved clinical indication.

Specific purity, analytical data (e.g., HPLC, NMR), and lot-specific certificates of analysis are available upon request from Aladdin Scientific.

Ordering PA-824 from Aladdin Scientific

PA-824 (Pretomanid) is available from Aladdin Scientific under product SKU P129923. Researchers and procurement teams can place orders through the Aladdin Scientific website or by contacting customer service directly.

When ordering, consider the following:

• Quantity: Select the pack size appropriate for your experimental needs. Bulk quantities may be available; contact Aladdin Scientific for custom quantity enquiries.
• Documentation: Certificates of Analysis (CoA), Safety Data Sheets (SDS), and technical datasheets are available for download on the product page or upon request.
• Shipping: The compound should be shipped under conditions that maintain stability. Confirm shipping and storage temperature requirements with Aladdin Scientific at the time of order.
• Regulatory compliance: Ensure your institution holds any required permits or licences for receipt and use of this compound, particularly if working with scheduled or controlled substances under local regulations.

For technical questions about PA-824, contact Aladdin Scientific technical support. For account, payment, and order management queries, refer to the Help and Customer Service section of the Aladdin Scientific website.