Oritavancin(LY-333328)是一种半合成脂糖肽类万古霉素类似物，可抑制ArlS激酶活性，IC50值为5.47μM。
Cas No.:171099-57-3
Sample solution is provided at 25 µL, 10mM.
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Oritavancin(LY-333328) is a semisynthetic lipoglycopeptide analogue of vancomycin, inhibiting ArlS kinase activity with an IC50 value of 5.47µM [1]. Oritavancin can bind to the d-alanyl-d-alanine peptidoglycan termini of Lipid II, prevent the cross-linking of adjacent peptidoglycan chains, reduce the integrity of the cell wall, and cause membrane depolarization and increased permeability in intact Staphylococcus and Enterococcus[2]. Oritavancin has been widely used to kill drug-resistant Gram-positive bacteria and alleviate acute bacterial skin and soft tissue infections[3].
In vitro, Oritavancin (20μg/ml) treatment for 24 hours significantly promoted the production of reactive oxygen species (ROS) in J774 cells exposed to H2O2[4]. Treatment with 20mg/ml Oritavancin for 72 hours resulted in the accumulation of phospholipids, free cholesterol, and esterified cholesterol in rat embryonic fibroblasts[5].
In vivo, Oritavancin treatment via daily subcutaneous injection at a dose of 50mg/kg for 10 days significantly reduced the load of pulmonary Mycobacterium abscessus in the immunosuppressed mouse models[6]. Daily intravenous administration of 10mg/kg dose of Oritavancin for 2 days significantly reduced the concentration of penicillin-resistant Streptococcus pneumoniae in the meningitis rabbit model and decreased inflammatory indicators[7].
References:
[1] Bai J, Zhu X, Zhao K, 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]. Emerging microbes & infections, 2019, 8(1): 503-515.
[2] Brade K D, Rybak J M, Rybak M J. Oritavancin: a new lipoglycopeptide antibiotic in the treatment of gram-positive infections[J]. Infectious diseases and therapy, 2016, 5(1): 1-15.
[3] Saravolatz L D, Stein G E. Oritavancin: a long-half-life lipoglycopeptide[J]. Clinical Infectious Diseases, 2015, 61(4): 627-632.
[4] Lemaire S, Mingeot-Leclercq M P, Tulkens P M, et al. Study of macrophage functions in murine J774 cells and human activated THP-1 cells exposed to oritavancin, a lipoglycopeptide with high cellular accumulation[J]. Antimicrobial agents and chemotherapy, 2014, 58(4): 2059-2066.
[5] Van Bambeke F, Saffran J, Mingeot-Leclercq M P, et al. Mixed-lipid storage disorder induced in macrophages and fibroblasts by oritavancin (LY333328), a new glycopeptide antibiotic with exceptional cellular accumulation[J]. Antimicrobial agents and chemotherapy, 2005, 49(5): 1695-1700.
[6] Wang G, Tang J, Feng J, et al. Activity of oritavancin and its synergy with other antibiotics against Mycobacterium abscessus infection in vitro and in vivo[J]. International Journal of Molecular Sciences, 2021, 22(12): 6346.
[7] Cabellos C, Fernandez A, Maiques J M, et al. Experimental study of LY333328 (oritavancin), alone and in combination, in therapy of cephalosporin-resistant pneumococcal meningitis[J]. Antimicrobial agents and chemotherapy, 2003, 47(6): 1907-1911.
Oritavancin(LY-333328)是一种半合成脂糖肽类万古霉素类似物，可抑制ArlS激酶活性，IC50值为5.47μM[1]。Oritavancin能与脂质II的d-alanyl-d-alanine肽聚糖末端结合，阻止相邻肽聚糖链的交联，降低细胞壁完整性，并在完整的葡萄球菌和肠球菌中引起膜去极化和通透性增加[2]。Oritavancin已被广泛用于杀灭耐药革兰氏阳性菌，并缓解急性细菌性皮肤和皮肤软组织感染[3]。
在体外，使用20µg/ml的Oritavancin处理暴露于H2O2的J774细胞24小时，显著促进了细胞内活性氧（ROS）的产生[4]。使用20mg/ml的Oritavancin处理大鼠胚胎成纤维细胞72小时，导致磷脂、游离胆固醇和酯化胆固醇的积累[5]。
在体内，每日皮下注射50mg/kg剂量的Oritavancin，持续10天，显著降低了免疫抑制小鼠模型中的肺Mycobacterium abscessus的细菌载量[6]。每日静脉注射10mg/kg剂量的Oritavancin，连续2天，显著降低了脑膜炎兔模型中青霉素耐药肺炎链球菌的浓度，并减少了炎症指标[7]。
| Cell experiment [1]: | |
Cell lines | J774 cells |
Preparation Method | J774 cells were cultured in RPMI 1640 containing 10% fetal calf serum at 37°C in a 5% CO2 humidified incubator. The cells were treated with different concentrations of Oritavancin (1, 5, 10, 20, 40, 60, 80, and 100μg/ml) for 24 hours, and then incubated in HBSS buffer containing 0.5% hydrogen peroxide for 25 minutes. The levels of ROS in the cells were evaluated. |
Reaction Conditions | 1, 5, 10, 20, 40, 60, 80, and 100μg/ml; 24h |
Applications | Oritavancin treatment significantly enhanced the levels of ROS in J774 cells exposed to H2O2 in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female BALB/c mice |
Preparation Method | Female BALB/c mice (6-week-old) were housed four per cage in a soundproof room under a 12h/12h light/dark cycle (lights on at 07:00) and were fed a standard laboratory diet and tap water ad libitum. Dexamethasone was administered by subcutaneous injection at 5 mg/kg/day (6 days per week) to suppress the immune response of mice to sustain M. abscessus infection. All mice were infected with 106 CFU M. abscessus via intravenous injection. From day 3 after infection, the infected mice were treated daily with Oritavancin for 10 days. Oritavancin, cefoxitin, and meropenem were administered via subcutaneous injection at the doses of 50mg/kg, 200mg/kg, and 100mg/kg, respectively. All the mice were sacrificed on day 10 after drug treatment, lungs were removed and homogenized. Homogenates were plated onto 7H11 agar plates to calculate CFUs for determining the bacterial loads of these organs. |
Dosage form | 50mg/kg/day for 10 days; s.c. |
Applications | Oritavancin treatment significantly reduced the load of pulmonary M. abscessu in the immunosuppressed mouse models. |
References: | |
| Cas No. | 171099-57-3 | SDF | |
| 别名 | 奥利万星 | ||
| Canonical SMILES | CC1C(C(CC(O1)OC2C3C(=O)NC(C4=CC(=CC(=C4C5=C(C=CC(=C5)C(C(=O)N3)NC(=O)C6C7=CC(=C(C(=C7)OC8=C(C=C(C=C8)C(C(C(=O)NC(C(=O)N6)CC(=O)N)NC(=O)C(CC(C)C)NC)O)Cl)OC9C(C(C(C(O9)CO)O)O)OC1CC(C(C(O1)C)O)(C)NCC1=CC=C(C=C1)C1=CC=C(C=C1)Cl)OC1=C(C=C2C=C1)Cl)O)O)O)C(=O)O) | ||
| 分子式 | C6H97Cl3N10O26 | 分子量 | 1793.120 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 557.7 μL | 2.7884 mL | 5.5769 mL |
| 5 mM | 111.5 μL | 557.7 μL | 1.1154 mL |
| 10 mM | 55.8 μL | 278.8 μL | 557.7 μL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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- Purity: >98.00% Appearance: A solid
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