VNRX-14079
VNRX-14079 is an antibacterial agent and PBP2 inhibitor, with an IC50 value of 1.7 μM against wild-type Neisseria gonorrhoeae PBP2. VNRX-14079 forms a covalent bond with Ser310 of PBP2, interacts with multiple residues of PBP2 to stabilize the complex, and induces an inward conformational change of the β3-β4 loop in chimeric PBP2. VNRX-14079 exhibits antibacterial activity against Ceftriaxone (HY-B0712)-resistant Neisseria gonorrhoeae strains. VNRX-14079 can be used in the research of gonorrhea.
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- CAS No.: 2872654-37-8
- Formule: C22H22BF2N4O12PS
- Masse moléculaire:646.28
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
VNRX-14079 binds to PBP2 of wild-type *Neisseria gonorrhoeae* (strain FA19) with an IC50 of 1.7 µM[1].
VNRX-14079 binds to chimeric Neisseria gonorrhoeae PBP2 from strain H041, with an IC50 of 3.0 µM[1].
VNRX-14079 (24 h) exhibits potent antibacterial activity against most Neisseria gonorrhoeae strains producing non-mosaic and mosaic PBP2[1].
VNRX-14079 (4× MIC-16× MIC; 2-24 h) exhibits rapid bactericidal activity against *Neisseria gonorrhoeae* ATCC 49226, WHO Q and H041. At 4× and 16× MIC, it reduces bacterial counts by ≥2 log10 within 6 hours and lowers them to undetectable levels within 24 hours[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCI BALB/c (female, 6-7 weeks old, pretreated with 17β oestradiol and antibiotics to suppress commensal microbiota, vaginally infected with ceftriaxone-resistant Neisseria gonorrhoeae H041)[1]
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Dosage:10 mg/kg; 200 mg/kg; 150 mg/kg
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Administration:s.c.; q12h (total 2 doses on day 1); q24h (single dose on day 1); q8h (total 3 doses on day 1)
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Result:Achieved 80% bacterial clearance by day 4 with statistically significant reduction in culture-positive mice relative to vehicle controls (P < 0.01) at 10 mg/kg q12h.
Achieved 100% clearance by day 3 with predicted 44% free unbound drug concentration above the MIC over 24 hours at 200 mg/kg q24h.
Resulted in 90% clearance by day 2 at 150 mg/kg q12h.
Achieved 100% clearance by day 2 at 150 mg/kg q8h.
Showed reduced average bacterial burden consistent with clearance rates across all doses.
Detected no evolution of spontaneous gonococcal mutants or adverse effects across all doses.
Chemical Information
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CAS No. 2872654-37-8
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Masse moléculaire 646.28
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Formule C22H22BF2N4O12PS
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SMILES
O=C(O)C1=C(F)C=CC(C2)=C1OB(O)[C@H]2NC([C@H](NC(N3C(N(S(=O)(C)=O)CC3)=O)=O)C4=CC=C(P(O)(O)=O)C(F)=C4)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Research Protocol for Infectious Diseases
Infectious-disease experiments test how pathogens interact with host barriers, innate immune receptors, inflammatory signaling, pathogen replication, and tissue injury; pattern-recognition receptors such as TLRs, RIG-I-like receptors, NOD-like receptors, and inflammasomes detect microbial molecules and activate NF-κB, interferon, and cytokine responses. The central hypothesis is that infection severity reflects the balance between pathogen burden and host response: protective inflammation restricts pathogen growth, whereas excessive or mislocalized inflammation contributes to tissue damage and disease phenotype. Unresolved questions include which host pathways are protective versus pathogenic, why some infection models fail to translate to human disease, and which combined readouts best predict clinically relevant infection outcomes.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Bacterial live/dead nucleic-acid viability staining
The LIVE/DEAD bacterial viability staining method is based on differential permeability of nucleic-acid-binding fluorescent dyes, most commonly SYTO 9 and propidium iodide (PI), which enables discrimination of bacterial populations with intact versus compromised cytoplasmic membranes. SYTO 9 penetrates both intact and damaged bacterial membranes and binds nucleic acids to produce green fluorescence, whereas propidium iodide penetrates only cells with compromised membranes and fluoresces red while also reducing SYTO 9 signal through competitive binding and fluorescence interactions. The resulting fluorescence pattern is interpreted as a proxy for membrane integrity, which is widely used as an indicator of bacterial viability in microscopy, flow cytometry, and spectroscopic platforms. However, mechanistic studies show that SYTO 9 and PI interactions involve displacement and fluorescence resonance energy transfer effects, which can influence signal interpretation depending on dye ratios a
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VNRX-14079 Related Classifications
HY-183080 Related Classifications
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