Tetracycline
55 clinical isolates of C. acnes are inhibited by seromycin. The drug's MIC values ranged from 0.5 to 16 µg/ml; the MIC50 was 0.5 µg/ml and the MIC90 was 4 µg/ml.Sarecycline works against organisms that are resistant to macrolides[1].
When it comes to enteric aerobic Gram-negative bacteria, serocycline hydrochloride shows very little activity[2].

血清霉素可抑制 55 种临床分离的痤疮丙酸杆菌。该药物的MIC值范围为0.5至16 µg/ml； MIC50 为 0.5 µg/ml，MIC90 为 4 µg/ml。Sarecycline 可对抗对大环内酯类药物具有抗性的微生物[1]。
对于肠道需氧革兰氏阴性菌，盐酸思瑞环素显示出很少的活性[ 2]。

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Sarecycline 对55株痤疮丙酸杆菌临床分离株表现出体外活性，MIC范围为0.5至16 µg/mL，MIC50为0.5 µg/mL，MIC90为4 µg/mL。此活性与四环素、多西环素和米诺环素相当。它对高水平耐红霉素（MIC ≥128 µg/mL）的痤疮丙酸杆菌亚群也保持活性。[1]
针对需氧革兰氏阳性球菌，Sarecycline 对甲氧西林敏感和耐药的金黄色葡萄球菌均显示活性（两者的MIC90均为0.5 µg/mL）。对表皮葡萄球菌，MIC90为2 µg/mL。它对溶血葡萄球菌的活性优于四环素和多西环素（MIC90：2 µg/mL）。对化脓性链球菌和无乳链球菌，MIC90值分别为8 µg/mL和16 µg/mL。[1]
对粪肠球菌（万古霉素敏感），Sarecycline 活性有限，MIC90为32 µg/mL。对尿肠球菌（包括万古霉素敏感和耐药菌株），MIC90值在16至32 µg/mL之间。[1]
针对需氧革兰氏阴性杆菌（肠杆菌科），Sarecycline 的活性显著低于广谱四环素类药物。对大肠杆菌，MIC90为>64 µg/mL（对照药为2-32 µg/mL）。对肺炎克雷伯菌，MIC90为>64 µg/mL。对奇异变形杆菌基本无活性（MIC >64 µg/mL）。针对另一组当代肠杆菌科分离株（来自11-40岁患者），与米诺环素和多西环素相比，Sarecycline 的效力降低（基于MIC50比较，低16至32倍）。[1]
针对代表性的革兰氏阳性厌氧菌（如双歧杆菌属、梭菌属、乳杆菌属），根据MIC分布图，Sarecycline 的效力比多西环素低4至8倍。针对革兰氏阴性厌氧菌（如拟杆菌属、普雷沃菌属），Sarecycline 是所测试的活性最低的四环素类药物。[1]
在使用金黄色葡萄球菌ATCC 29213的巨分子生物合成实验中，Sarecycline 以浓度依赖性方式抑制蛋白质合成，在8倍MIC时达到约80%的抑制。在此浓度下，它对DNA、RNA、脂质和细胞壁合成的影响最小。[1]
针对痤疮丙酸杆菌的自发突变频率研究表明，Sarecycline 在4倍和8倍MIC下的突变频率较低（约10^-10），与米诺环素和万古霉素相似。针对金黄色葡萄球菌和表皮葡萄球菌，在4倍和8倍MIC下的频率范围为10^-9至10^-8，与万古霉素相似。[1]
针对耐四环素的金黄色葡萄球菌菌株，Sarecycline 对携带外排基因tet(K)的菌株（MIC范围：0.125-1 µg/mL）比四环素（16-64 µg/mL）更具活性。然而，其对携带核糖体保护基因tet(M)（MIC：8 µg/mL）或同时携带tet(M)和tet(38)（MIC：16-32 µg/mL）的菌株活性降低。[1]

在中性粒细胞减少性大腿感染的小鼠模型中，盐酸沙雷环素（0.33-9 mg/kg；静脉注射）对金黄色葡萄球菌表现出强大的功效[1]。

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在小鼠系统性腹腔感染模型中，单次皮下剂量的Sarecycline 对金黄色葡萄球菌RN450-1显示出疗效，50%保护剂量（PD50）为0.25 mg/kg，与多西环素（PD50：0.3 mg/kg）相当，但效力低于米诺环素（PD50：0.03 mg/kg）。[1]
在同一模型中对大肠杆菌PBS1478，Sarecycline 即使在最高测试剂量40 mg/kg下也未显示出疗效（PD50 >40 mg/kg），而多西环素和米诺环素的PD50值分别为5.72 mg/kg和6.95 mg/kg。[1]
在小鼠中性粒细胞减少大腿感染模型中，针对金黄色葡萄球菌RN450-1，静脉注射Sarecycline 实现了细菌负荷降低2-log10，ED50为8.23 mg/kg，与多西环素（ED50：8.31 mg/kg）相当。[1]

描述的主要基于细胞的实验是标准抗菌药敏试验。对于厌氧菌（包括痤疮丙酸杆菌），根据指南使用参考琼脂稀释法。细菌在适当的琼脂平板（如用于痤疮丙酸杆菌的布鲁氏菌琼脂）上于厌氧条件下培养。将抗生素系列稀释液掺入琼脂中。平板接种标准化的细菌悬液并厌氧培养（例如，痤疮丙酸杆菌在35°C下培养48小时）。MIC定义为抑制肉眼可见生长的最低浓度。[1]
对于需氧菌，使用参考肉汤微量稀释法。在微量滴定板中，于阳离子调节的MH肉汤中制备抗生素的系列二倍稀释液。将细菌悬液调整至0.5麦氏单位标准并稀释至最终接种密度。将稀释后的悬液加入孔中。平板在有氧条件下（例如，35°C培养18-24小时）孵育，读取无肉眼可见生长的最低浓度作为MIC。[1]
巨分子生物合成实验在生长至指数早期的金黄色葡萄球菌ATCC 29213培养物中进行。为了评估对DNA、RNA或蛋白质合成的影响，将含有Sarecycline（在MIC的倍数下）的培养物孵育5分钟，然后加入放射性标记的前体（[³H]胸苷、[³H]尿苷或[³H]亮氨酸）。反应在室温下进行15-30分钟，并通过加入冰冷的三氯乙酸终止。收集沉淀物，并使用液体闪烁计数器测量放射性。对于细胞壁和脂质合成，遵循类似的程序，分别使用[³H]N-乙酰葡糖胺和[³H]甘油作为前体。[1]

Animal Model: Female SD-1 mice (A murine neutropenic thigh wound infection model)[1]
Dosage: 0.33, 1, 3, or 9 mg/kg
Administration: Intravenously
Result: at a dose similar to doxycycline, achieved a 2-log10 reduction in the bacterial burden in the thigh (ED50s of 8.23 and 8.32 mg/kg, respectively).

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1. Murine Systemic Intraperitoneal Infection Model: Six-week-old, specific-pathogen-free, male CD-1 mice (up to 30 g) were used. For S. aureus RN450-1 infection, bacteria were grown overnight in Mueller-Hinton broth to ~1x10^9 CFU/mL, diluted in phosphate-buffered saline (PBS), and mixed with a 5% bacteriological mucin suspension. Mice were infected intraperitoneally with 3.5x10^8 to 7.4x10^8 CFU. For E. coli PBS1478 infection, a similar process was used, with an inoculum of 6.5x10^7 to 1.6x10^8 CFU. At 1 hour post-infection, mice were treated subcutaneously with a single dose of Sarecycline, doxycycline, or minocycline dissolved in sterile water. Doses were adjusted for the active moiety percentage. Doses ranged from 0.01 to 0.5 mg/kg for S. aureus studies and from 0.5 to 40 mg/kg for E. coli studies. Survival was monitored for 48 hours to determine the PD50 (dose required for 50% survival). [1]
2. Murine Neutropenic Thigh Infection Model: Female SD-1 mice were rendered neutropenic by intraperitoneal injections of cyclophosphamide (150 mg/kg on day -4 and 100 mg/kg on day -1). On day 0, mice were infected by intramuscular injection of 1x10^6 CFU of S. aureus RN450-1 into the left thigh. At 2 and 6 hours post-infection, mice were treated intravenously with Sarecycline or doxycycline at doses of 0.33, 1, 3, or 9 mg/kg in sterile water. At 24 hours post-infection, thighs were removed, homogenized, and plated on trypticase soy agar with 5% sheep blood to determine bacterial burden. The ED50 was defined as the dose required to achieve a 2-log10 reduction in CFU compared to the untreated control. [1]

Sarecycline is administered orally once daily at 1.5 mg/kg, with or without food, as no difference in bioavailability was observed with food intake. It is less likely to cross the blood-brain barrier compared to other tetracyclines. Specific PK parameters such as half-life, oral bioavailability, absorption, distribution, metabolism, and excretion are not provided. [2]

In Phase III studies, the most common adverse events included nausea (3.2% in sarecycline vs. 1.7% in placebo), nasopharyngitis, headache, and vomiting. Vulvovaginal candidiasis/mycotic infection was reported in 1.1–1.2% of sarecycline-treated subjects. No cases of phototoxicity, dizziness, pseudotumor cerebri, tinnitus, vertigo, or esophagitis were significantly increased compared to placebo. [2]

[1]. Antimicrob Agents Chemother. 2018;63(1):e01297-18.

[2]. Future Microbiol. 2019;14(14):1235-1242.

[3]. Proc Natl Acad Sci U S A. 2020;117(34):20530-20537.

[4]. J Drugs Dermatol.2018 Mar 1;17(3):333-338.

See also: Sarecycline Hydrochloride (annotation moved to).

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Sarecycline is described as the first narrow-spectrum tetracycline-class antibiotic developed specifically for the treatment of moderate to severe acne vulgaris. It is an oral aminomethylcycline with a unique modification at the C-7 position. [1]
It completed two phase 3 clinical trials, meeting the 12-week primary efficacy endpoint for acne treatment. [1]
Its narrow spectrum of activity, with reduced potency against aerobic enteric Gram-negative bacteria and intestinal anaerobic flora compared to broad-spectrum tetracyclines like doxycycline and minocycline, is proposed to potentially lead to less disruption of the gut microbiome and associated adverse effects (e.g., diarrhea, candidiasis). [1]
The antimicrobial action against C. acnes is via inhibition of protein synthesis, which may also downregulate the production of inflammatory proteins/enzymes, contributing to an anti-inflammatory effect. [1]

C24H30CLN3O8

523.97

523.172

C, 55.02; H, 5.77; Cl, 6.77; N, 8.02; O, 24.43

1035979-44-2

Sarecycline;1035654-66-0

71296095

Light yellow to yellow solid powder

1.908

174.85

6

10

5

36

1010

4

O([H])[C@@]12C(=C(C(N([H])[H])=O)C([C@]([H])([C@]1([H])C([H])([H])[C@]1([H])C([H])([H])C3=C(C([H])([H])N(C([H])([H])[H])OC([H])([H])[H])C([H])=C([H])C(=C3C(=C1C2=O)O[H])O[H])N(C([H])([H])[H])C([H])([H])[H])=O)O[H]

APPRLAGZQKOUFL-FIPJBXKNSA-N

InChI=1S/C24H29N3O8.ClH/c1-26(2)18-13-8-11-7-12-10(9-27(3)35-4)5-6-14(28)16(12)19(29)15(11)21(31)24(13,34)22(32)17(20(18)30)23(25)33;/h5-6,11,13,18,28,30-31,34H,7-9H2,1-4H3,(H2,25,33);1H/t11-,13-,18-,24-;/m0./s1

(4S,4aS,5aR,12aS)-4-(dimethylamino)-3,10,12,12a-tetrahydroxy-7-((methoxy(methyl)amino)methyl)-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide hydrochloride

WC-3035 HCl; WC 3035 hydrochloride; WC3035; P005672 hydrochloride; P-005672; P 005672; P005672; trade name: Seysara

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

DMSO : ~100 mg/mL (~190.85 mM)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。