Zosurabalpin TFA
Zosurabalpin (Abx MCP; RG6006) TFA is a lipopolysaccharide (LPS) transport inhibitor that targets the LptB2FGC complex. Zosurabalpin TFA blocks the transport of LPS from the inner membrane to the outer membrane, leading to intracellular toxic accumulation of LPS and bacterial death. Zosurabalpin TFA exhibits potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii (CRAB) and shows in vivo efficacy in mouse infection models. Zosurabalpin TFA can be used for research on CRAB infections, including pneumonia and sepsis.
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- Formule: C43H50N8O5S.xC2HF3O2
- Masse moléculaire:790.97 (free base)
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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
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
Zosurabalpin (Abx MCP; RG6006) TFA potently inhibits multidrug-resistant Acinetobacter baumannii isolates in vitro by targeting the LptB2FGC LPS transport complex, with MIC values ranging from 0.12 to 1.00 μg/mL[2].
Zosurabalpin (0.01-10 μM; 10 min) TFA inhibits LPS transport by targeting the LptB2FGC complex of Acinetobacter baylyi, with detectable inhibitory effects observed at concentrations as low as 0.01 μM[3].
Zosurabalpin (24 h) TFA exerts bactericidal activity against pan-drug-resistant Acinetobacter baumannii ACC01073 at concentrations of 4× MIC and above[3].
Zosurabalpin (0.01-10 μM; 60 min) TFA inhibits the transport of lipopolysaccharide (LPS) from wild-type A. baylyi LptB2FGC to LptA[4].
Zosurabalpin (0.0001-10 μM) TFA binds to LPS-loaded A. baylyi LptB2FG with high affinity (but does not bind to LptB2FGC)[4].
Zosurabalpin TFA sequesters LPS in the intermediate transport state of A. baylyi LptB2FG by binding to the composite site formed by the transporter and its LPS substrate, and its binding conformation competes with the transmembrane helix of LptC for access to the transporter gate[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 (Elimination) |
|---|---|---|---|---|---|
| Mice[3] | 1 mg/kg | i.v. | 51 mL/min/kg | 0.7 L/kg | 0.3 h |
In Vivo
Zosurabalpin (24-48 h) TFA achieves a net reduction in bacteria within 24 hours and sustains suppression of bacterial loads over 48 hours at different administration doses in neutropenic mouse thigh and lung models of Acinetobacter baumannii infection[1].
Zosurabalpin (0.3-30 mg/kg; subcutaneous injection; administered twice at 1 h and 5 h post-infection) TFA confers 100% survival rate to immunocompetent mice with Acinetobacter baumannii-induced sepsis at doses of 1 mg/kg and above[3].
Zosurabalpin (6-360 mg/kg; subcutaneous injection; once every 6 hours; for 24 hours) TFA reduces lung bacterial load by > 5 log10 in neutropenic mice infected with extensively drug-resistant A. baumannii pneumonia at a total daily subcutaneous dose of 360 mg/kg[3].
Zosurabalpin (6-360 mg/kg; subcutaneous injection; once every 6 hours; for 24 hours) TFA reduces the thigh bacterial load of neutropenic mice with thigh infections induced by multidrug-resistant A. baumannii below the limit of detection at total daily subcutaneous doses of 160 mg/kg and above[3].
Zosurabalpin (30 mg/kg; subcutaneous injection; 2 administrations) TFA confers complete or partial survival benefits to immunocompetent mice infected with a specific Zosurabalpin-resistant A. baumannii mutant strain[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1 (male, 6 weeks old at arrival, immunocompetent, inoculated intraperitoneally with carbapenem-resistant Acinetobacter baumannii ACC00445)[3]
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Dosage:0.3, 1, 3, 10, 30 mg/kg
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Administration:s.c.; 2 doses at 1 and 5 h post-infection
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Result:Achieved 100% mouse survival over 7 days at 1 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg.
Achieved 10% mouse survival over 7 days at 0.3 mg/kg.
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Animal Model:CD-1 (male, 6 weeks old at arrival, neutropenic via two intraperitoneal injections of cyclophosphamide monohydrate on day -4 and day -1, inoculated intratracheally with pan-drug-resistant Acinetobacter baumannii ACC01073)[3]
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Dosage:6, 20, 60, 160, 240, 360 mg/kg
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Administration:s.c.; every 6 hours; 24 hours
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Result:Caused a dose-dependent decrease in lung bacterial burden.
Achieved a > 5 log10 reduction in CFUs at the 360 mg/kg per day dose.
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Animal Model:CD-1 (male, 6 weeks old at arrival, neutropenic via two intraperitoneal injections of cyclophosphamide monohydrate on day -4 and day -1, inoculated intramuscularly with multidrug-resistant Acinetobacter baumannii ACC01085)[3]
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Dosage:6, 20, 60, 160, 240, 360 mg/kg
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Administration:s.c.; every 6 hours; 24 hours
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Result:Caused a dose-dependent decrease in thigh bacterial burden.
Achieved reductions below the limit of detection (2 log10 CFUs per thigh) at doses of 160 mg/kg per day and above.
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Animal Model:CD-1 (male, 6 weeks old at arrival, immunocompetent, inoculated intraperitoneally with zosurabalpin-resistant Acinetobacter baumannii mutants)[3]
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Dosage:30 mg/kg
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Administration:s.c.; 2 doses
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Result:Achieved 100% survival for mice infected with adeS R152K, adeS G318S, adeS R108S, and adeS ISAba1 mutants.
Achieved 87.5% survival for mice infected with the lptG G40D mutant.
Achieved 75% survival for mice infected with the adeS ISAba1 (ROB23370) mutant.
Achieved 50% survival for mice infected with the lptF R322C mutant.
Achieved 37.5% survival for mice infected with the lptF W271S mutant.
Achieved 0% survival for mice infected with the lptF I323K, lptF I317L, and lptF R322L mutants.
Chemical Information
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Masse moléculaire 790.97 (free base)
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Formule C43H50N8O5S.xC2HF3O2
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SMILES
O=C1NCC2=C(C3=CC=C(C=C3)C(O)=O)C=CC=C2SC4=NC=CC=C4CN[C@H](C(N[C@H](C(N([C@H]1CC5=CNC6=CC=CC=C56)C)=O)CCCCN)=O)CCCN.OC(C(F)(F)F)=O.[x]
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Synonyms
Abx MCP TFA; RG6006 TFA
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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.
Pureté et documentation
Références
[3]. Zampaloni C, et al. A novel antibiotic class targeting the lipopolysaccharide transporter. Nature. 2024 Jan;625(7995):566-571. [Content Brief]
[4]. Pahil KS, et al. A new antibiotic traps lipopolysaccharide in its intermembrane transporter. Nature. 2024 Jan;625(7995):572-577. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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