Oritavancin  (Synonyms: LY 333328; Orbactiv)

Oritavancin (LY 333328), a semisynthetic derivative of Vancomycin (HY-B0671), is an orally active glycopeptide antibiotic with bactericidal activity against gram-positive organisms. Oritavancin shows antibacterial effect against B. anthracis, such as Ames strain with a MIC value of 0.015 g/mL. Oritavancin inhibits cell wall synthesis and disrupts the membrane potential. Oritavancin inhibits ArlS kinase activity thereby interfering the signal transduction. Oritavancin enters cells by adsorptive endocytosis, which drives it to lysosomes, where it exerts antibiotic activity^{[1][2][3][4][5]}.

Oritavancin (25 μM, 30 min) dose-dependently inhibits the kinase activity of ArlS (3 μg) by 98% with an IC⁵⁰ value of 5.47 μΜ in vitro^[1].
Oritavancin (0.7 μM, 42 h) decreases spx expression in the USA300-Pspx strain^[1].
Oritavancin (3.1 μM, 24 h) disrupts mature MRSA biofilms and facilitates bactericidal activity of Oritavancin and Oxacillin (HY-B0925A) against embedded S. aureus cells^[1].
Oritavancin’ (0-80 μg/mL, 2 h) incubation with increasing extracellular concentrations and the uptake by cells proceed in an cooperative manner in J774 macrophages^[2].
Oritavancin (25 mg/L, 24 h) exerts a marked bactericidal effect against intracellular S. aureus^[2].

Oritavancin accumulation by different cell types^[2]

(The cells were incubated for 2 h at 37°C with 25 mg of the drug per liter in a medium containing 10% FCS)^[2]

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Oritavancin (i.p. for 1 and 3 mg/kg or i.v. for 15 and 50 mg/kg, every 48 h for 14 days or a single dose for 30 days) provides significant protection in the mouse inhalation anthrax model^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1793.10

C₈₆H₉₇Cl₃N₁₀O₂₆

171099-57-3

O[C@@H]1[C@@H](O[C@@](O[C@@H](C)[C@@H]2O)([H])C[C@]2(C)NCC3=CC=C(C4=CC=C(Cl)C=C4)C=C3)[C@@H](O[C@H](CO)[C@H]1O)OC5=C(OC6=CC=C([C@H]([C@H]7NC([C@H](NC)CC(C)C)=O)O)C=C6Cl)C=C([C@](NC([C@@H](NC7=O)CC(N)=O)=O)([H])C(N[C@](C8=O)([H])C9=CC%10=C(O)C=C9)=O)C=C5OC%11=CC=C([C@H]([C@](C(N[C@@](C(O)=O)([H])C%12=C%10C(O)=CC(O)=C%12)=O)([H])N8)O[C@@](O[C@@H](C)[C@@H]%13O)([H])C[C@@]%13(N)C)C=C%11Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Bai J, et al. The role of ArlRS in regulating oxacillin susceptibility in methicillin-resistant Staphylococcus aureus indicates it is a potential target for antimicrobial resistance breakers[J]. Emerg Microbes Infect. 2019;8(1):503-515.  [Content Brief]

  [2]. Van Bambeke F, et al. Cellular pharmacokinetics and pharmacodynamics of the glycopeptide antibiotic oritavancin (LY333328) in a model of J774 mouse macrophages[J]. Antimicrob Agents Chemother. 2004 Aug;48(8):2853-60.  [Content Brief]

  [3]. Heine HS, et al. Efficacy of oritavancin in a murine model of Bacillus anthracis spore inhalation anthrax. Antimicrob Agents Chemother. 2008 Sep;52(9):3350-7.  [Content Brief]

  [4]. Coyle EA, et al. Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model. Antimicrob Agents Chemother. 2001 Mar;45(3):706-9.  [Content Brief]

  [5]. Arhin FF, et al. Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing. Antimicrob Agents Chemother. 2008 May;52(5):1597-603.  [Content Brief]