β-lactam
Penicillin-Binding Protein 2 (PBP 2) of Staphylococcus aureus (IC₅₀ ~ 0.1 µg/ml at 4°C; IC₅₀ > 10 µg/ml at 37°C in competition assay due to rapid deacylation) [1]
Penicillin-Binding Protein 3 (PBP 3) of Staphylococcus aureus (IC₅₀ for direct labeling ~ 0.025 µg/ml; > 90% saturation at 0.1 µg/ml in competition assay) [1]
Penicillin-Binding Protein 1 (PBP 1) of Staphylococcus aureus (90% saturation at 0.06 µg/ml in direct labeling assay) [1]

在使用金黄色葡萄球菌209P菌株膜制剂的竞争性结合实验中，Cefaclor特异性结合PBP 3，在37°C孵育15分钟后，0.1 µg/ml浓度下饱和度 > 90%。相同条件下，与PBP 2的结合很弱（在1和10 µg/ml浓度下饱和度分别为9%和34%）。[1]
使用[³H]Cefaclor对膜样品进行直接放射性标记实验表明，Cefaclor与多种PBP具有高亲和力结合。在37°C孵育15分钟后，达到90%饱和度所需的浓度分别为：PBP 1需0.06 µg/ml，PBP 2需0.3 µg/ml，PBP 3需0.025 µg/ml。[1]
研究发现了Cefaclor与PBP 2结合后快速脱酰基的特性。Cefaclor酰基-PBP 2复合物在37°C下的半衰期约为10分钟，而在4°C下则 > 120分钟。这种药物从PBP 2上的快速释放解释了在37°C下进行的竞争性实验中观察到的表观低亲和力结合。[1]
通过Mueller-Hinton肉汤中的宏观稀释法测定，Cefaclor对金黄色葡萄球菌209P菌株的最低抑菌浓度（MIC）为1 µg/ml。[1]
在生长抑制研究中，浓度为0.05、0.125和0.25 µg/ml的Cefaclor（在竞争性实验中能特异性饱和PBP 3但不结合PBP 2）单独使用时未引起细胞裂解。然而，当与克拉维酸（5 µg/ml，可饱和PBP 2）联用时，0.05 µg/ml的Cefaclor显著增强了细胞裂解。单独使用0.25 µg/ml的Cefaclor产生的细胞裂解效果与联合用药相似。[1]
通过非平衡pH梯度电泳分离的两种PBP 2肽段（酸性和碱性）的分析显示，在4°C下，两种肽段都以相似的高亲和力结合Cefaclor（两者的IC₅₀均约0.1 µg/ml）。在37°C下，酸性肽段的表观亲和力较低（IC₅₀为20.5 µg/ml），而碱性肽段的IC₅₀为2 µg/ml，这可能归因于脱酰基速率的差异。[1]

使用两种主要方法评估了Cefaclor与青霉素结合蛋白的结合亲和力：竞争性实验和直接放射性标记实验。[1]
对于竞争性实验，将金黄色葡萄球菌的膜或全细胞制剂与不同浓度的未标记Cefaclor预孵育指定时间（例如，37°C下30分钟）。随后，样品用[³H]penicillin G（5 µg/ml）在特定时间段内（例如，37°C或4°C下15分钟）进行放射性标记。通过加入变性缓冲液停止反应以进行电泳。结合的PBP通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分离，并通过荧光自显影显示。通过扫描光密度法测量特定PBP的放射性标记强度相对于对照样品（未与未标记药物预孵育）的降低，用于计算饱和百分比和抑制浓度（IC₅₀, IC₉₀）。通过在4°C（减缓脱酰基）和37°C下进行放射性标记步骤，专门研究了温度对结合和脱酰基的影响。[1]
对于直接放射性标记实验，膜样品直接与不同浓度的[³H]Cefaclor（例如，0.025至1 µg/ml）在37°C下孵育15分钟。停止反应后，通过SDS-PAGE分离PBP，并通过荧光自显影显示以确定直接结合饱和度水平。[1]
Cefaclor-PBP 2复合物的脱酰基速率（半衰期）通过以下方法确定：将膜样品与未标记Cefaclor（1 µg/ml）在37°C下预孵育30分钟，随后在37°C或4°C下用[³H]penicillin G进行不同时间（1至120分钟）的放射性标记。在37°C下，放射性标记的PBP 2随时间增加表明结合的Cefaclor被释放并被[³H]penicillin G取代，从而可以计算脱酰基半衰期。[1]

Absorption, Distribution and Excretion
Absorbed well after oral administration, unaffected by food intake. Approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours, with the majority excreted within the first 2 hours. Metabolism/Metabolites No significant biotransformation occurs in the liver (approximately 60% to 85% of the drug is excreted unchanged in the urine within 8 hours). Biological Half-Life 0.6–0.9 hours

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Cefaclor has been discontinued in the United States. Limited information suggests that low concentrations of the drug in breast milk are not expected to have adverse effects on breastfed infants after mothers have taken cefaclor. There have been reports that cephalosporins occasionally disrupt the gut microbiota of infants, leading to diarrhea or thrush, but these effects have not been fully assessed. It is safe for breastfeeding women to take cefaclor.
◉ Effects on Breastfed Infants
In a telephone follow-up study, 5 breastfeeding mothers reported taking cefaclor (dosage not specified). One mother reported that her infant developed diarrhea. No rashes or candidiasis were reported in the exposed infants.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding 23.5%

[1]. Characterization of penicillin-binding protein 2 of Staphylococcus aureus: deacylation reaction and identification of two penicillin-binding peptides. Antimicrob Agents Chemother. 1992 Mar;36(3):656-61.

[2]. Cefaclor revisited. Clin Ther. 2000 Feb;22(2):154-66.

[3]. Pharmacokinetic profile of cefaclor. Int J Clin Pharmacol Ther .

Cefaclor is a cephalosporin with a chlorine atom at position 3 and an (R)-2-amino-2-phenylacetamide group at positions 7 of its cephalosporin backbone. It is both an antibacterial drug and a drug allergen. It is a semi-synthetic broad-spectrum antibiotic derivative of cephalexin. Anhydrous cefaclor is a cephalosporin antibacterial drug. Cefaclor is a second-generation β-lactam cephalosporin antibiotic with bactericidal activity. Cefaclor binds to and inactivates penicillin-binding protein (PBP) located on the bacterial cell membrane. PBP is an enzyme involved in the final stages of bacterial cell wall assembly and in remodeling the cell wall during bacterial growth and division. Inactivation of PBP interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of the bacterial cell wall. This leads to weakening of the bacterial cell wall and cell lysis. Anhydrous cefaclor is the anhydrous form of cefaclor, a second-generation β-lactam cephalosporin with antibacterial activity. Cefaclor binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of bacterial cell walls. Inactivation of PBPs interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This leads to weakened bacterial cell walls and cell lysis. Cefaclor is a semi-synthetic broad-spectrum antibiotic and a derivative of cefalexin. Indications Used to treat certain bacterial infections, such as pneumonia, as well as infections of the ear, lungs, skin, throat, and urinary tract. FDA Label Mechanism of Action Like penicillin antibiotics, cefaclor is a β-lactam antibiotic. It inhibits the third (and final) stage of bacterial cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. Subsequently, bacterial cell wall autolysins (such as autolysins) mediate cell lysis. Cefaclor may interfere with the action of autolysin inhibitors.

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Pharmacodynamics
Cefaclor is a second-generation cephalosporin antibiotic with an antibacterial spectrum similar to first-generation cephalosporins. In vitro Studies have shown that the bactericidal effect of cephalosporins stems from the inhibition of cell wall synthesis. In vitro and in vivo clinical studies have demonstrated that cefaclor is effective against most Gram-positive aerobic bacteria—Staphylococci (including coagulase-positive, coagulase-negative, and penicillinase-producing strains), Streptococcus pneumoniae, Streptococcus pyogenes (Group A hemolytic streptococci) and Gram-negative aerobic bacteria—Escherichia coli, Haemophilus influenzae (including β-lactamase-producing ampicillin-resistant strains), Klebsiella spp., and Proteus mirabilis. Cefaclor is a β-lactam antibiotic. This study focuses on the interaction between cefaclor and penicillin-binding proteins (PBPs) in Staphylococcus aureus. [1]
A key finding is that cefaclor binds to PBP2 with high affinity, but this binding is characterized by rapid deacylation (drug release from the enzyme complex) at physiological temperatures (37°C) with a half-life of approximately 10 minutes. This characteristic could lead to an underestimation of its binding affinity in standard competitive assays if the radiolabeling step is prolonged. [1]
The study also found that PBP2 consists of two distinct penicillin-binding peptides (an acidic peptide and a basic peptide), which can be separated by isoelectric focusing, and both peptides can bind to cefaclor. [1]
The antibacterial activity of cefaclor against Staphylococcus aureus is related to its binding to PBP2 (as well as PBP1 and PBP3), resolving the previous paradox of cefaclor being effective even when it does not bind to PBP2 in conventional assays. [1]

C15H14CLN3O4S

367.81

367.039

C, 48.98; H, 3.84; Cl, 9.64; N, 11.42; O, 17.40; S, 8.72

53994-73-3

Cefaclor monohydrate;70356-03-5;Cefaclor-d5;1426173-90-1

51039

Light yellow to yellow solid powder

1.6±0.1 g/cm3

713.4±60.0 °C at 760 mmHg

385.2±32.9 °C

0.0±2.4 mmHg at 25°C

1.722

0.1

138.03

3

6

4

24

606

3

O=C(C(N12)=C(Cl)CS[C@]2([H])[C@H](NC([C@H](N)C3=CC=CC=C3)=O)C1=O)O

QYIYFLOTGYLRGG-GPCCPHFNSA-N

InChI=1S/C15H14ClN3O4S/c16-8-6-24-14-10(13(21)19(14)11(8)15(22)23)18-12(20)9(17)7-4-2-1-3-5-7/h1-5,9-10,14H,6,17H2,(H,18,20)(H,22,23)/t9-,10-,14-/m1/s1

(6R,7R)-7-[[(2R)-2-amino-2-phenylacetyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

S6472; Cefaclor Anhydrous; Ceclor; Lilly 99638; Monohydrate, Cefaclor;Cefaclorum; Cephaclor; Raniclor; Kefral; Cefaclor Monohydrate; Keclor; S 6472; S-6472;

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)

DMSO : ~18.5 mg/mL (~50.30 mM)
H2O : ~3.85 mg/mL (~10.47 mM)

配方 1 中的溶解度: 3.33 mg/mL (9.05 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。 (<60°C).

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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。