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PAβN dihydrochloride (MC-207110; Phe-Arg-β-naphthylamide) is a novel and potent efflux pump inhibitor, acting on the MDR (multidrug resistance) efflux pump/transporters of some Gram-negative bacteria.
Physicochemical Properties
| Molecular Formula | C₂₅H₃₂CL₂N₆O₂ |
| Molecular Weight | 519.47 |
| Exact Mass | 518.196 |
| Elemental Analysis | C, 57.80; H, 6.21; Cl, 13.65; N, 16.18; O, 6.16 |
| CAS # | 100929-99-5 |
| PubChem CID | 90665180 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 6.055 |
| Hydrogen Bond Donor Count | 7 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 35 |
| Complexity | 659 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| InChi Key | MRUMOHLDHMZGMS-ZZYOSWMOSA-N |
| InChi Code | InChI=1S/C25H30N6O2.2ClH/c26-21(15-17-7-2-1-3-8-17)23(32)31-22(11-6-14-29-25(27)28)24(33)30-20-13-12-18-9-4-5-10-19(18)16-20;;/h1-5,7-10,12-13,16,21-22H,6,11,14-15,26H2,(H,30,33)(H,31,32)(H4,27,28,29);2*1H/t21-,22+;;/m1../s1 |
| Chemical Name | (S)-2-((R)-2-amino-3-phenylpropanamido)-5-guanidino-N-(naphthalen-2-yl)pentanamide dihydrochloride |
| Synonyms | PAßN dihydrochloride; PAßN-dihydrochloride; PAssN 2HCl; PAssN-2HCl; MC-207110 2HCl; MC207110 2HCl; MC 207110 2HCl; Phe-Arg β-naphthylamide; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | PAβN increases the susceptibilities of the three pump-overexpressing mutants of P. aeruginosa to levofloxacin 64-fold. Moreover, PAβN increases the efficacy of levofloxacin against strain PAM2391, which carries the plasmid pAGH97 containing the mexXY genes, as well as against strain PAM1020, which is the wild type. The susceptibilities to other antibiotics that are substrates of efflux pumps are impacted by PAβN. The accumulation of efflux pump substrates within the cell is increased by PAβN. It increases levofloxacin's efficacy against P. aeruginosa clinical isolates[1]. In nine ciprofloxacin-resistant isolates, PAβN lowers the MICs; in four of these, PAβN doubles the susceptibility.Furthermore, PAβN makes five of the isolates resistant to ciprofloxacin susceptible again. Furthermore, for twenty of these isolates that are resistant to ciprofloxacin, there are evident effects of NMP on the MICs[2]. When using PAβN as a control for efflux studies, it is important to take into account its additional mode of action, as it permeabilizes bacterial membranes in a concentration-dependent manner at levels lower than those usually employed in combination studies[3]. |
| References |
[1]. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob Agents Chemother. 2001 Jan;45(1):105-16. [2]. Effects of efflux pump inhibitors on erythromycin, ciprofloxacin, and tetracycline resistance in Campylobacter spp. isolates. Microb Drug Resist. 2012 Oct;18(5):492-501. [3]. The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PAβN) permeabilizes the outer membrane of gram-negative bacteria. PLoS One. 2013;8(3):e60666. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~160.41 mM) H2O : ~14.29 mg/mL (~27.51 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9250 mL | 9.6252 mL | 19.2504 mL | |
| 5 mM | 0.3850 mL | 1.9250 mL | 3.8501 mL | |
| 10 mM | 0.1925 mL | 0.9625 mL | 1.9250 mL |