| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
DNA Gyrase Subunit B (GyrB). SPR719, the active metabolite of SPR720 disodium, is a potent inhibitor of bacterial DNA gyrase (topoisomerase II), an essential enzyme involved in DNA replication, transcription, and repair. Unlike fluoroquinolones that target GyrA, SPR719 binds to the ATP-binding site of GyrB, blocking ATP hydrolysis and preventing DNA supercoiling. This unique mechanism of action results in bactericidal activity against both replicating and non-replicating mycobacteria.
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| ln Vitro |
Not applicable (SPR720 is a prodrug that is converted to SPR719 in vivo; in vitro activity is assessed using the active metabolite). SPR719 (the active metabolite) exhibits potent activity against Mycobacterium tuberculosis (Mtb) with MIC values in the low micromolar range. It also shows activity against nontuberculous mycobacteria (NTM) including M. avium, M. abscessus, and M. kansasii. The compound demonstrates a novel mechanism of action distinct from fluoroquinolones and has no cross-resistance with existing anti-TB drugs.
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| ln Vivo |
In a mouse model of chronic tuberculosis infection, fobrepodacin disodium (oral gavage; 10, 30, 100 mg/kg; once daily; five times per week for four weeks) lowers the mycobacterial burden [1]. The oral dosage of fobrepodacin disodium (100 mg/kg) administered once daily for eight weeks on five days a week boosts the antimycobacterial drugs' bactericidal action [1].
SPR720 disodium reduces the mycobacterial burden in a mouse model of chronic tuberculosis infection. Oral administration of SPR720 disodium (100 mg/kg; once per day; 5 days per week for 8 weeks) improves the bactericidal activities of antimycobacterial drugs. The prodrug is rapidly absorbed and converted to SPR719, achieving therapeutic concentrations in plasma and lung tissue. SPR720 disodium has potent bactericidal activity in vivo against both drug-sensitive and drug-resistant M. tuberculosis strains. |
| Enzyme Assay |
Not applicable (the active metabolite SPR719 is the pharmacologically active species, measured in biochemical assays). DNA gyrase supercoiling assays are performed using purified M. tuberculosis GyrA and GyrB subunits. Gyrase (50-100 nM) is incubated with varying concentrations of SPR719 (0.01-100 microM) in reaction buffer (35 mM Tris-HCl pH 7.5, 24 mM KCl, 4 mM MgCl2, 2 mM DTT, 1.8 mM spermidine, 1 mM ATP, 0.36 mg/mL BSA) for 30-60 minutes at 37degC. The reaction is initiated by adding relaxed pBR322 plasmid DNA (0.5 microg). After termination, DNA is resolved by agarose gel electrophoresis, and supercoiled DNA is quantified by densitometry. IC50 values are calculated.
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| Cell Assay |
Not applicable (cell-based activity is measured for SPR719, the active metabolite). M. tuberculosis H37Rv cultures are grown in Middlebrook 7H9 broth with OADC enrichment to mid-log phase. Bacteria are diluted to 1-5 × 10⁵ CFU/mL and added to 96-well plates containing varying concentrations of SPR719 (0.01-100 microM). Plates are incubated at 37degC for 5-7 days. The MIC (minimum inhibitory concentration) is defined as the lowest concentration resulting in ≥90% inhibition of growth compared to drug-free controls, measured by visual inspection or by resazurin reduction assay (fluorescence, excitation 530 nm, emission 590 nm).
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| Animal Protocol |
Animal/Disease Models: uninfected or Mycobacterium tuberculosis-infected sixweeks old female BALB/c and C57BL/6 mice (Erdman) [1]
Doses: 10, 30, 100 mg/kg Route of Administration: po (oral gavage); daily Once; 5 times per week for 4 weeks Experimental Results: diminished mycobacterial load in a mouse model of chronic tuberculosis infection. Female BALB/c mice (6-8 weeks, 18-22 g) are infected intravenously or intratracheally with M. tuberculosis H37Rv (1-5 × 10⁵ CFU/mouse) to establish a chronic tuberculosis infection model. After 2-4 weeks of infection (to establish chronic disease), mice are randomized into treatment groups (n=8-10). SPR720 disodium is formulated in 0.5% methylcellulose or other vehicle and administered orally at 50-200 mg/kg once daily, 5 days per week, for 4-8 weeks. At study termination, lungs, spleen, and liver are harvested, homogenized, and serial dilutions are plated on 7H11 agar. CFU (colony-forming units) are counted after 3-4 weeks of incubation at 37degC. The reduction in bacterial burden (log10 CFU/organ) compared to vehicle control is calculated. |
| ADME/Pharmacokinetics |
SPR720 disodium is an orally bioavailable phosphate prodrug (F ≈ 30-50%) that is rapidly converted to the active moiety SPR719 in vivo. Following oral administration in rodents (100 mg/kg), peak plasma concentrations (Cmax) of SPR720 are reached within 0.5-1 hour, with rapid conversion to SPR719. SPR719 has a terminal half-life of approximately 4-8 hours and achieves high concentrations in lung tissue (the primary site of TB infection). The prodrug design improves aqueous solubility and oral absorption compared to the parent compound.
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| Toxicity/Toxicokinetics |
SPR720 disodium is an investigational antibacterial agent; preclinical and clinical safety data have been reported. In Phase 1 clinical trials, SPR720 was generally well tolerated with a safety profile consistent with other antibacterial agents. The most common adverse events reported include mild to moderate gastrointestinal disturbances (nausea, diarrhea, abdominal pain) and headache. No significant hepatotoxicity or cardiotoxicity (QTc prolongation) was observed. SPR720 disodium is not approved by the FDA as of 2025.
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| References | |
| Additional Infomation |
SPR720 disodium (Fobrepodacin disodium) is a novel oral antibacterial prodrug under clinical development for the treatment of nontuberculous mycobacterial (NTM) infections, particularly M. avium complex (MAC) lung disease. It received Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA. SPR720 works through a unique gyrase B inhibition mechanism, providing a new treatment option for drug-resistant mycobacterial infections. The compound is for research use and clinical development; it is not a commercially available drug.
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| Molecular Formula |
C21H24FN6NA2O6P
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|---|---|
| Molecular Weight |
552.403570175171
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| Exact Mass |
552.127
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| CAS # |
1384984-20-6
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| Related CAS # |
SPR719;1384984-18-2;Fobrepodacin;1384984-31-9
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| PubChem CID |
71451278
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
785
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| Defined Atom Stereocenter Count |
1
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| SMILES |
P(=O)([O-])([O-])OC(C)(C)C1N=CC(=CN=1)C1=CC2=C(C(=C1F)[C@H]1CCCO1)N=C(NC(NCC)=O)N2.[Na+].[Na+]
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| InChi Key |
BSOLRSNBVIVVMJ-FMOMHUKBSA-L
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| InChi Code |
InChI=1S/C21H26FN6O6P.2Na/c1-4-23-20(29)28-19-26-13-8-12(16(22)15(17(13)27-19)14-6-5-7-33-14)11-9-24-18(25-10-11)21(2,3)34-35(30,31)32;;/h8-10,14H,4-7H2,1-3H3,(H2,30,31,32)(H3,23,26,27,28,29);;/q;2*+1/p-2/t14-;;/m1../s1
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| Chemical Name |
disodium;2-[5-[2-(ethylcarbamoylamino)-6-fluoro-7-[(2R)-oxolan-2-yl]-3H-benzimidazol-5-yl]pyrimidin-2-yl]propan-2-yl phosphate
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| Synonyms |
SPR720 disodium; SPR-720 disodium
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~5 mg/mL (~9.05 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8103 mL | 9.0514 mL | 18.1028 mL | |
| 5 mM | 0.3621 mL | 1.8103 mL | 3.6206 mL | |
| 10 mM | 0.1810 mL | 0.9051 mL | 1.8103 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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