isoleucyl t-RNA synthetase
Bacterial isoleucyl-tRNA synthetase (IleRS) [1][2]

莫匹罗星 (BRL-4910A) 对葡萄球菌和链球菌以及某些革兰氏阴性菌具有高水平的活性。莫匹罗星 (BRL-4910A) 与人血清蛋白高度结合（95% 结合），在人血清存在下活性降低 10 至 20 倍

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葡萄球菌属抗菌活性：莫匹罗星（BRL-4910A）对甲氧西林敏感金黄色葡萄球菌（MSSA）、甲氧西林耐药金黄色葡萄球菌（MRSA）及表皮葡萄球菌（包括万古霉素中介菌株）具有强效浓度依赖性抗菌活性。最低抑菌浓度（MIC）范围为：MSSA 0.03-0.12 μg/mL、MRSA 0.06-0.25 μg/mL、表皮葡萄球菌 0.03-0.5 μg/mL [1][5]
- 作用机制：特异性抑制细菌异亮氨酸-tRNA合成酶（IleRS），阻断异亮氨酸的活化及其与对应tRNA的氨酰化反应。在MIC浓度下，该作用可在4-6小时内完全抑制靶细菌生长[2]
- 无交叉耐药性：在MRSA及多重耐药表皮葡萄球菌菌株中，与β-内酰胺类、万古霉素、大环内酯类等其他类别抗生素无交叉耐药性，证实其作用机制独特[5]
- 抗菌谱局限：对革兰氏阴性菌（如大肠杆菌、铜绿假单胞菌）和厌氧菌活性微弱或无活性，MIC值＞32 μg/mL [1]

莫匹罗星口服和肠胃外给药后吸收良好，但由于广泛降解为无抗菌活性的代谢物莫尼酸 A，因此血清抗生素浓度维持时间较短。

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小鼠MRSA浅表皮肤伤口感染：将莫匹罗星（BRL-4910A）制成0.2%（w/w）软膏，每日两次局部涂抹小鼠皮肤伤口，连续5天，较未治疗对照组，伤口MRSA载量降低3-4 log10 CFU/伤口。药物可加速伤口愈合，减轻局部炎症和水肿[3]
- 大鼠血管移植物感染预防：血管移植物植入前，用1%（w/w）莫匹罗星（BRL-4910A）溶液浸泡30分钟，可使接受腹主动脉吻合术的大鼠中，表皮葡萄球菌（甲氧西林敏感、MRSA、万古霉素中介菌株）的移植物感染发生率降低70-80%[5]
- 全身给药无抗菌疗效：腹腔注射、静脉注射等全身给药方式因全身吸收极少，无显著体内抗菌活性[2]

细菌异亮氨酸-tRNA合成酶（IleRS）活性检测:
1. 纯化重组金黄色葡萄球菌IleRS，制备[³H]标记的异亮氨酸和tRNAIle作为反应底物。
2. 将IleRS、[³H]-异亮氨酸、tRNAIle与系列浓度（0.01-1 μg/mL）的莫匹罗星（BRL-4910A）在反应缓冲液（50 mM Tris-HCl pH 7.5，10 mM MgCl₂，2 mM ATP）中于37°C孵育30分钟。
3. 加入5%三氯乙酸终止反应，过滤混合物以保留结合了[³H]-异亮氨酸的tRNA，去除未掺入的核苷酸。
4. 液体闪烁计数法测量保留部分的放射性，定量IleRS介导的氨酰化反应抑制效率[2]

细胞系：金黄色葡萄球菌
浓度：0-100 μM/mL
孵育时间：24、48 小时
结果：24 小时后减少 90% 至 99%，MIC 值范围为 0.12- 48 小时时，1.0 μM/mL 和 MBC 值范围为 4.0-32 μM/mL。

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最低抑菌浓度（MIC）测定（肉汤稀释法）:
1. 在Mueller-Hinton肉汤中制备系列浓度（0.001-64 μg/mL）的莫匹罗星（BRL-4910A）。
2. 向每个浓度梯度中接种MSSA、MRSA或表皮葡萄球菌（含万古霉素中介菌株）的菌悬液（1×10⁵ CFU/mL）。
3. 37°C孵育18-24小时后，肉眼观察细菌生长情况，无可见细菌生长的最低药物浓度即为MIC[1][5]
- 抗菌谱琼脂扩散实验:
1. 在Mueller-Hinton琼脂平板上均匀涂布菌苔（MSSA、MRSA、大肠杆菌）。
2. 将浸泡过莫匹罗星（BRL-4910A）（10 μg/片）的无菌滤纸片置于琼脂表面。
3. 37°C孵育24小时后，测量滤纸片周围透明抑菌圈的直径，评估抗菌活性[1]

MRSA skin infection model in mice (10-12 weeks old)
2% ointment
External administration; twice daily; 3-6 days

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Murine MRSA superficial skin wound infection model:
1. Create 6 mm full-thickness dorsal skin wounds on BALB/c mice (6-8 weeks old), then inoculate each wound with 1×10⁶ CFU of MRSA.
2. Randomly divide mice into an untreated control group and a treatment group (n=8 per group).
3. Formulate Mupirocin (BRL-4910A) as a 0.2% (w/w) ointment and apply it topically to the wounds twice daily for 5 days.
4. On day 5, excise the wound tissues, homogenize them in sterile saline, and plate serial dilutions of the homogenate on agar plates to count bacterial colonies (CFU/wound). Assess wound healing by measuring wound area and performing histopathological analysis of inflammation and tissue regeneration [3]
- Rat vascular-graft infection prophylaxis model:
1. Implant polyurethane vascular grafts into male Wistar rats (250-300 g) via abdominal aorta anastomosis.
2. Prior to implantation, soak the grafts in Mupirocin (BRL-4910A) solution (1% w/w) for 30 minutes (treatment group) or sterile saline (control group).
3. Inoculate the graft implantation site with 1×10⁶ CFU of S. epidermidis (methicillin-susceptible, MRSA, or vancomycin-intermediate strain).
4. Four weeks after implantation, harvest the grafts, culture them for bacterial growth, and calculate the infection incidence by comparing the number of infected grafts in the treatment and control groups [5]

Absorption, Distribution and Excretion
In adults and children, systemic or transdermal absorption of mupirocin is expected to be minimal following transdermal administration. Occlusive dressings do not significantly enhance drug absorption, but damaged skin may allow the drug to more easily penetrate the skin barrier. Any mupirocin that enters systemic circulation is rapidly metabolized to inactive monosodium monoxide and excreted via the kidneys. In 23 healthy volunteers, after applying 2% Centany (mupirocin ointment) once daily to a 400 cm² area on the back for 7 consecutive days, the mean (range) cumulative excretion of monosodium monoxide in urine within 24 hours after the last dose was 1.25% (0.2% to 3.0%) of the administered dose. No information available. No information available. Metabolism/Metabolites Following intravenous or oral administration, mupirocin is rapidly metabolized in the liver to the major metabolite monosodium monoxide, which has no antibacterial activity.

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Biological half-life
In healthy male volunteers, the elimination half-life of mupirocin after intravenous injection is approximately 20 to 40 minutes. The elimination half-life of monic acid is approximately 30 to 80 minutes. Absorption: Systemic absorption after topical administration is minimal—<0.3% of the dose is absorbed through intact skin and <1% through broken skin. Oral bioavailability is <5% due to degradation in the gastrointestinal tract[2]. Distribution: It mainly remains at the site of topical administration, with negligible distribution to systemic tissues. Plasma concentrations after standard topical administration are below the limit of detection (<0.01 μg/mL)[2]. Metabolism: It is metabolized in the skin and liver to inactive metabolites, primarily monic acid derivatives[2]. Excretion: More than 60% of the absorbed dose is excreted in the urine as metabolites within 24 hours. The plasma elimination half-life of the absorbed drug is 2–4 hours[2].

Effects During Pregnancy and Lactation
◉ Overview of medication use during lactation
Mupirocin poses a low risk to breastfed infants due to its absorption rate of less than 1% after topical application. [1] Ensure that the infant's skin does not come into direct contact with the treated area. Only water-soluble creams or gels should be applied to the breast, as ointments may expose the infant to high concentrations of mineral oil through licking. [2] Topical application of mupirocin appears to be relatively ineffective for treating nipple pain and cracking.
◉ Effects on breastfed infants
A mother of a 52-day-old exclusively breastfed infant developed a soft tissue infection. She received intravenous teicoplanin at 400 mg every 12 hours for 3 times, followed by 400 mg daily for 5 days; intravenous ceftriaxone 1 g daily; and topical mupirocin cream twice daily. Careful follow-up showed that her infant did not experience any adverse reactions. [3]
◉ Effects on breastfeeding and breast milk
A small, randomized, nonblinded trial of mothers with nipple pain and cracking showed that applying 2% mupirocin cream to the nipples after each feeding (16%) was far less effective than oral antibiotics (cloxacillin or erythromycin for 10 days) (79%). Furthermore, a higher percentage of patients using mupirocin experienced worsening of their condition compared to those using oral antibiotics (28% vs. 5%). [4]
In a randomized, double-blind trial, researchers compared the effectiveness of lanolin versus a general nipple ointment containing 1% mupirocin, 0.05% betamethasone, and 2% miconazole in relieving nipple pain during the first two weeks of breastfeeding postpartum. Both treatments were comparable in reducing nipple pain, shortening nipple healing time, prolonging breastfeeding duration, increasing exclusive breastfeeding rates, reducing mastitis and nipple symptoms, decreasing side effects, or increasing maternal satisfaction with treatment. [5]

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Protein binding
It has been reported that the protein binding rate of mupirocin exceeds 95%.

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Local toxicity: 5-8% of the tested mice experienced mild and transient skin irritation (erythema, pruritus), which resolved spontaneously within 24 hours without interruption of administration. [3]
- Porcine skin toxicity: Topical application of 1% (w/w) mupirocin (BRL-4910A) for 14 days did not cause significant epidermal thickening, inflammation, cytotoxicity, or allergic contact dermatitis in porcine skin. [4]
- Systemic toxicity: No significant systemic toxicity (hepatotoxicity/nephrotoxicity) was observed. Dysfunction and hematological abnormalities were observed in rats and pigs after topical administration at 10 times the therapeutic dose. Serum transaminases, creatinine, and white blood cell counts were all within the normal range. [2][4]
- Mutagenicity and teratogenicity: No evidence of mutagenicity was found in the bacterial reverse mutation assay, and no teratogenicity was observed in pregnant rats. [2]

[1]. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother. 1985 Apr;27(4):495-8.

[2]. Mupirocin: a topical antibiotic with a unique structure and mechanism of action. Clin Pharm. 1987 Oct;6(10):761-70.

[3]. Efficacy of topical and systemic antibiotic treatment of meticillin-resistant Staphylococcus aureus in a murine superficial skin wound infection model. Int J Antimicrob Agents. 2013 Sep. 42(3):272-5.

[4]. Investigating auranofin for the treatment of infected diabetic pressure ulcers in mice and dermal toxicity in pigs. Sci Rep. 2021 May 25;11(1):10935.

[5]. Mupirocin prophylaxis against methicillin-susceptible, methicillin-resistant, or vancomycin-intermediate Staphylococcus epidermidis vascular-graft infection. Antimicrob Agents Chemother. 2000 Oct. 44(10):2842-4.

Mupirocin is an α,β-unsaturated ester formed by the condensation of the hydroxyl group of 9-hydroxynonanoic acid with the carboxyl group of (2E)-4-[(2S)-tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoic acid, wherein the 3- and 4-positions of the tetrahydropyran ring are substituted with hydroxyl groups, and the 5-position is substituted with {(2S,3S)-3-[(2S,3S)-3-hydroxybut-2-yl]ethyleneoxy-2-yl}methyl. It was initially isolated from the Gram-negative bacterium Pseudomonas fluorescens and used as a topical antibiotic to treat Gram-positive bacterial infections. It is both a bacterial metabolite and an antibacterial agent, and also has the effect of inhibiting protein synthesis. It is a monocarboxylic acid, belonging to the oxacyclohexane class of compounds, and is also an epoxide, secondary alcohol, triol, and α,β-unsaturated carboxylic acid ester. It is the conjugate acid of mupirocin (1-). Mupirocin, formerly known as Pseudomonas aeruginosa acid A, is a novel antibacterial agent with a unique chemical structure and mechanism of action, distinct from other antibiotics. Produced by the fermentation of Pseudomonas fluorescens, mupirocin is a naturally occurring antibiotic with broad-spectrum antibacterial activity against a wide range of Gram-positive and some Gram-negative bacteria in vitro. Its primary mechanism of action is the inhibition of bacterial protein synthesis. Due to its unique mechanism of action of inhibiting bacterial isoleucyl-tRNA synthetase activity, mupirocin does not exhibit cross-resistance with other antibacterial agents, giving it a therapeutic advantage. Because of its extensive systemic metabolism, mupirocin is only available in topical formulations for the treatment of impetigo caused by Staphylococcus aureus and Streptococcus pyogenes, as well as traumatic skin lesions caused by secondary skin infections of Staphylococcus aureus and Streptococcus pyogenes. Some clinical evidence suggests that intranasal administration of mupirocin may help clear staphylococci from the nasal cavity. A common brand name for mupirocin is Bactroban. Mupirocin is an RNA synthase inhibitor. Its mechanism of action is as an RNA synthase inhibitor. Mupirocin has been reported to exist in Pseudomonas fluorescens, and relevant data are available. Mupirocin is a natural crotonic acid derivative extracted from Pseudomonas fluorescens. Mupirocin inhibits bacterial protein synthesis by specifically and reversibly binding to bacterial isoleucine-tRNA synthetase. It has excellent activity against Gram-positive staphylococci and streptococci, and is mainly used to treat primary and secondary skin diseases, nasal infections, and promote wound healing. (NCI04) A topical antibiotic derived from Pseudomonas fluorescens. It exhibits excellent activity against Gram-positive staphylococci and streptococci. This antibiotic is mainly used to treat primary and secondary skin diseases, nasal infections, and wound healing.

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Drug Indications
Indications for the treatment of impetigo and secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes, leading to traumatic skin lesions. Mechanism of Action Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer RNA (tRNA) synthase, which promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme, in turn, inhibits bacterial protein and RNA synthesis. Mupirocin exhibits antibacterial activity at low concentrations, but prolonged exposure can exert bactericidal effects, killing 90-99% of susceptible bacteria within 24 hours. Pharmacodynamics Mupirocin has been reported to be effective against susceptible aerobic Gram-positive cocci (such as Staphylococcus aureus and Staphylococcus epidermidis) and other β-hemolytic streptococci (such as Streptococcus pyogenes). Its antibacterial activity is achieved by inhibiting bacterial protein synthesis and the formation of proteins essential for bacterial survival. The minimum bactericidal concentration (MBC) against relevant pathogens is typically 8 to 30 times higher than the minimum inhibitory concentration (MIC). In a clinical study investigating the efficacy of topical mupirocin in treating impetigo, the response rate one week after treatment completion was approximately 94% to 98%. In clinical studies of patients with primary and secondary skin infections, over 90% of patients receiving topical mupirocin treatment demonstrated pathogen clearance and clinical cure or symptom improvement. Mupirocin resistance rates as high as 81% have been previously reported. Mupirocin resistance is more common in methicillin-resistant Staphylococcus aureus (MRSA) than in methicillin-sensitive MRSA, and its development may be due to the production of a modified isoleucyl-tRNA synthetase or the acquisition of a plasmid mediating a novel isoleucyl-tRNA synthetase through gene transfer. Mupirocin (BRL-4910A) is a natural antibiotic produced by Pseudomonas fluorescens, specifically developed for topical clinical use.[1][2]
- Mechanism of action: It binds specifically to bacterial isoleucyl-tRNA synthetase (IleRS) with high affinity, preventing the activation of isoleucine and its subsequent binding to tRNAIle. This blocks bacterial protein synthesis, leading to growth inhibition and ultimately bacterial death.[1][2]
- Clinical indications: It is approved for the treatment of superficial skin infections (e.g., impetigo, folliculitis) caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). It is also used to prevent vascular graft infections and decolonization of Staphylococcus aureus (including MRSA) in the nasal cavity [5] - Selectivity advantage: It has 1000 times higher affinity for bacterial IleRS than human IleRS, thereby minimizing off-target effects on mammalian cells [2] - Resistance: Inherent resistance is rare; acquired resistance is associated with mutations in the bacterial ileS gene (encoding IleRS) and occurs at a low rate in clinical settings [5]

C26H44O9

500.62

500.298

C, 62.38; H, 8.86; O, 28.76

12650-69-0

73346-79-9;115074-43-6;104486-81-9

446596

White to off-white solid powder

1.2±0.1 g/cm3

672.3±55.0 °C at 760 mmHg

77-780C

216.5±25.0 °C

0.0±4.7 mmHg at 25°C

1.524

3.44

146.05

4

9

17

35

694

8

O1[C@@]([H])([C@@]([H])(C([H])([H])[H])[C@]([H])(C([H])([H])[H])O[H])[C@]1([H])C([H])([H])[C@@]1([H])C([H])([H])O[C@@]([H])(C([H])([H])/C(=C(\[H])/C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(=O)O[H])/C([H])([H])[H])[C@@]([H])([C@]1([H])O[H])O[H]

MINDHVHHQZYEEK-HBBNESRFSA-N

InChI=1S/C26H44O9/c1-16(13-23(30)33-11-9-7-5-4-6-8-10-22(28)29)12-20-25(32)24(31)19(15-34-20)14-21-26(35-21)17(2)18(3)27/h13,17-21,24-27,31-32H,4-12,14-15H2,1-3H3,(H,28,29)/b16-13+/t17-,18-,19-,20-,21-,24+,25-,26-/m0/s1

9-[(E)-4-[(2S,3R,4R,5S)-3,4-dihydroxy-5-[[(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl]methyl]oxan-2-yl]-3-methylbut-2-enoyl]oxynonanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.99 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.99 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.99 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。