PAβN dihydrochloride (MC-207,110 dihydrochloride)
(Synonyms: 苯丙氨酸-精氨酸-Β-萘胺,MC-207,110 dihydrochloride; Phe-Arg-β-naphthylamide dihydrochloride) 目录号 : GC32063
PAβN dihydrochloride (MC-207,110 dihydrochloride)是一种肽模拟化合物，是一种广谱细菌外排泵抑制剂（EPI）。
Cas No.:100929-99-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PAβN dihydrochloride (MC-207,110 dihydrochloride) is a peptide mimetic compound that is a broad-spectrum bacterial efflux pump inhibitor (EPI)[1]. PAβN dihydrochloride is the first inhibitor of the resistance nodule cell differentiation (RND) family of efflux pumps in Gram-negative bacteria[2]. PAβN dihydrochloride reduces the resistance of Pseudomonas aeruginosa to fluoroquinolones[3]. PAβN dihydrochloride can cause a 2- to 2048-fold decrease in the MIC of antimicrobial agents known to be substrates of the CmeABC pump in all Campylobacter strains[4]. PAβN dihydrochloride can be used to evaluate the efficacy of new EPI candidates[5].
In vitro, treatment of Salmonella typhimurium cells with PAβN dihydrochloride (32μM) inhibited efflux activity, increased the accumulation of ethidium (Et+) and tetraphenylphosphine (TPP+) in cells, and stimulated Et+ fluorescence[6].
References:
[1] Y Mahmood H, Jamshidi S, Mark Sutton J, et al. Current advances in developing inhibitors of bacterial multidrug efflux pumps[J]. Current medicinal chemistry, 2016, 23(10): 1062-1081.
[2] Compagne N, Vieira Da Cruz A, Müller R T, et al. Update on the discovery of efflux pump inhibitors against critical priority Gram-negative bacteria[J]. Antibiotics, 2023, 12(1): 180.
[3] Rahbar M, Hamidi-Farahani R, Asgari A, et al. Expression of RND efflux pumps mediated antibiotic resistance in Pseudomonas aeruginosa clinical strains[J]. Microbial Pathogenesis, 2021, 153: 104789.
[4] Martinez A, Lin J. Effect of an efflux pump inhibitor on the function of the multidrug efflux pump CmeABC and antimicrobial resistance in Campylobacter[J]. Foodbourne Pathogens & Disease, 2006, 3(4): 393-402.
[5] Blankson G A. Structure-activity studies on bacterial efflux inhibitors[M]. Rutgers The State University of New Jersey, School of Graduate Studies, 2016.
[6] Sakalauskaitė S, Mikalayeva V, Daugelavičius R. Ethidium binding to Salmonella enterica ser. Typhimurium Cells and Salmon sperm DNA[J]. Molecules, 2021, 26(11): 3386.
PAβN dihydrochloride (MC-207,110 dihydrochloride)是一种肽模拟化合物，是一种广谱细菌外排泵抑制剂（EPI）[1]。PAβN dihydrochloride是革兰氏阴性菌中耐药结节细胞分化家族（RND）外排泵的第一个抑制剂[2]。PAβN dihydrochloride降低铜绿假单胞菌对氟喹诺酮类药物的耐药性[3]。PAβN dihydrochloride能够导致所有弯曲杆菌菌株中已知为CmeABC泵底物的抗菌剂的MIC降低2至2048倍[4]。PAβN dihydrochloride能够用于评估新EPI候选物的效率[5]。
在体外，PAβN dihydrochloride（32μM）处理鼠伤寒沙门氏菌细胞，可抑制外排活性，增加细胞中乙锭（Et+）和四苯基磷（TPP+）的积累并刺激Et+荧光[6]。
| Cas No. | 100929-99-5 | SDF | |
| 别名 | 苯丙氨酸-精氨酸-Β-萘胺,MC-207,110 dihydrochloride; Phe-Arg-β-naphthylamide dihydrochloride | ||
| Canonical SMILES | O=C([C@H](CCCNC(N)=N)NC([C@H](CC1=CC=CC=C1)N)=O)NC2=CC(C=CC=C3)=C3C=C2.Cl.Cl | ||
| 分子式 | C25H32Cl2N6O2 | 分子量 | 519.47 |
| 溶解度 | DMSO : ≥ 100 mg/mL (192.50 mM);Water : 14.29 mg/mL (27.51 mM) | 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 | 1.925 mL | 9.6252 mL | 19.2504 mL |
| 5 mM | 0.385 mL | 1.925 mL | 3.8501 mL |
| 10 mM | 0.1925 mL | 0.9625 mL | 1.925 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A multidrug efflux pump inhibitor reduces fluoroquinolone resistance in Pseudomonas aeruginosa isolates
Chemotherapy 2004 Apr;50(1):22-6.PMID:15084801DOI:10.1159/000077280.
In general, resistance to fluoroquinolones (FQs) in gram-negative bacteria is acquired either by mutations in DNA gyrase and topoisomerase IV or by active export of the agents via antibiotic efflux pumps. Reduced porin expression is also proposed to be another mechanism leading to resistance. In this study, interaction between levofloxacin, ofloxacin, and ciprofloxacin with MC-207,110 (multidrug efflux pump inhibitor) was investigated by a checkerboard assay using Pseudomonas aeruginosa. Levofloxacin, ofloxacin, and ciprofloxacin were tested at different concentrations (0.06-64 microg/ml) and MC-207,110 was tested at a concentration range of 4-128 microg/ml. In the presence of MC-207,110 (at 128, 64, 32, 16 microg/ml) resistance to FQs was inhibited significantly and MIC values were decreased, except at 8 and 4 microg/ml of MC-207,110. When MC-207,110 was used, resistance of P. aeruginosa to FQs in vitro was inhibited significantly, suggesting that MC-207,110 may be useful for use in clinical treatment protocols to overcome FQs resistance.
Efflux pumps may play a role in tigecycline resistance in Burkholderia species
Int J Antimicrob Agents 2010 Aug;36(2):151-4.PMID:20399621DOI:10.1016/j.ijantimicag.2010.03.009.
The purpose of this study was to investigate the role of multidrug resistance efflux pumps in relation to decreased susceptibility to tigecycline in clinical isolates of Burkholderia cepacia complex (BCC). The role of efflux pumps was analysed using the efflux pump inhibitor (EPI) MC-207,110. Minimum inhibitory concentrations (MICs) were determined for each strain against tigecycline alone and in the presence of 64 mg/L MC-207,110. The effect of efflux pump inhibition on the susceptibility of BCC isolates to tigecycline was assessed by a checkerboard titration assay. Ala-Nap uptake assay was performed to determine efflux pump activity in different strains. The checkerboard titration assay showed that the MIC decreased with increasing concentrations of EPI. MICs for tigecycline in the clinical isolates ranged between 8 mg/L and 32 mg/L, whereas in the presence of MC-207,110, MICs decreased significantly (range <0.125-1.0mg/L; 16 to >256 times reduction). Efflux pump activity was shown to be greatest in strains with the highest MIC and vice versa. In conclusion, BCC possess efflux pumps that influence their resistance to tigecycline. Use of an inhibitor of these pumps restored sensitivity to the antibiotic. Therefore, a combination of tigecycline and EPI to augment its efficacy may present an attractive therapeutic option.
Effect of efflux pump inhibitors on bile resistance and in vivo colonization of Campylobacter jejuni
J Antimicrob Chemother 2006 Nov;58(5):966-72.PMID:16963459DOI:10.1093/jac/dkl374.
Objectives: The multidrug efflux pump CmeABC is essential for Campylobacter colonization in animal intestine by mediating bile resistance. The objective of this study is to examine the effect of inhibition of the CmeABC pump by efflux pump inhibitor (EPI) on the susceptibility of Campylobacter to bile salts and to evaluate the in vivo efficacy of two EPIs on the colonization of Campylobacter in a host. Methods: Two wild-type Campylobacter jejuni strains and their isogenic cmeB mutants were used to determine the susceptibilities of the strains to various bile salts in the presence of EPI MC-207,110 or MC-04,124. The in vivo effect of the EPIs on the colonization of C. jejuni in a host was evaluated using a chicken model system. Results: The presence of EPIs resulted in a 16- to 512-fold reduction in the MICs of bile salts in both C. jejuni strains. Compared with wild-type strains, cmeB mutants displayed much smaller magnitudes of reduction in the MICs of bile salts, indicating that the in vitro effect of the EPI is primarily mediated by the CmeABC efflux pump. Investigation of 21 Campylobacter isolates from various origins further showed that the EPI MC-207,110 decreased bile resistance in all isolates. Single oral administration of EPI (MC-207,110 or MC-04,124) at two different doses reduced colonization of C. jejuni in chickens at 2-4 days post-inoculation only. Oral administration of MC-207,110 for three consecutive days following inoculation of C. jejuni did not result in a more significant reduction in the level of Campylobacter colonization in chickens. Conclusions: Inhibition of Campylobacter efflux pumps by EPIs is a potential means for therapeutic intervention to reduce colonization of C. jejuni in humans and animal reservoirs.
Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC
Chem Biol 2011 Apr 22;18(4):454-63.PMID:21513882DOI:10.1016/j.chembiol.2011.02.011.
Multidrug efflux pumps adversely affect both the clinical effectiveness of existing antibiotics and the discovery process to find new ones. In this study, we reconstituted and characterized by surface plasmon resonance the assembly of AcrAB-TolC, the archetypal multidrug efflux pump from Escherichia coli. We report that the periplasmic AcrA and the outer membrane channel TolC assemble high-affinity complexes with AcrB transporter independently from each other. Antibiotic novobiocin and MC-207,110 inhibitor bind to the immobilized AcrB but do not affect interactions between components of the complex. In contrast, DARPin inhibits interactions between AcrA and AcrB. Mutational opening of TolC channel decreases stability of interactions and promotes disassembly of the complex. The conformation of the membrane proximal domain of AcrA is critical for the formation of AcrAB-TolC and could be targeted for the development of new inhibitors.
Effect of an efflux pump inhibitor on the function of the multidrug efflux pump CmeABC and antimicrobial resistance in Campylobacter
Foodborne Pathog Dis 2006 Winter;3(4):393-402.PMID:17199521DOI:10.1089/fpd.2006.3.393.
CmeABC, a multidrug efflux pump, contributes to the resistance of Campylobacter to a broad range of antimicrobials. We hypothesize that an efflux pump inhibitor (EPI) may inhibit the function of CmeABC and control antibiotic resistance in Campylobacter. In this study, we examined the effect of EPI Phe-Arg beta-naphthyl-amide dihydrochloride (MC-207,110) on the susceptibility of Campylobacter to various antimicrobials. The presence of the EPI resulted in a 2- to 2048-fold reduction in the minimum inhibitory concentration (MIC) of antimicrobials known to be substrates of the CmeABC pump in all Campylobacter strains. Both intrinsic and acquired resistance of C. jejuni to erythromycin was decreased drastically (64- to 128-fold reduction in the MIC) in the presence of the EPI while the MICs of fluoroquinolones were only slightly decreased (2- to 4-fold). Examination of 57 Campylobacter isolates from various origins further demonstrated that MC-207,110 decreased the MICs of erythromycin (2- to 512-fold) in all isolates. Compared to wild-type strains, the isogenic CmeB mutants displayed smaller magnitudes of reduction in the MICs of antimicrobials in the presence of the EPI, indicating the inhibitory effect of the EPI is primarily CmeABC-dependent. The inhibitory effect of MC-207,110 was also dose-dependent, and as little as 0.5 microg/mL of the EPI resulted in a decreased MIC for erythromycin in C. jejuni. More importantly, the presence of MC-207,110 decreased the frequency of emergence of erythromycin-resistant mutants in C. jejuni (<10(11), well below the normal frequency of approximately 10(8)). Together, these findings indicate that EPI MC-207,110 inhibits the function of CmeABC efflux pump and potentiates the activity of antibiotics against Campylobacter. Inhibition of CmeABC by EPI is a promising approach in combating antibiotic resistance of Campylobacter in humans and animal reservoirs.