Polymyxin b nonapeptide hydrochloride

• CAS: 86408-36-8
• Catalog Number: ACM86408368
• Category: Main Products
• Molecular Weight: 2392.93
• Molecular Formula: C₁₁₁H₁₉₄N₃₂O₂₆
• Synonyms: POLYMYXIN B NONAPEPTIDE HYDROCHLORIDE;polymyxinbnonapeptide;N2-(L-Thr-L-A2bu-)Cyclo(L-A2bu*-L-A2bu-D-Phe-L-Leu-L-A2bu-L-A2bu-L-Thr-);N2-(L-Thr-L-A2bu-)Cyclo(L-A2bu*-L-A2bu-D-Phe-L-Leu-L-A2bu-L-A2bu-Thr-);Nα-(L-Thr-L-A2bu-)Cyclo(L-A2bu*-L-A2bu-D-Phe-L-Leu-L-A2bu-L-A2bu-L-Thr-);PMBN;sPMBN
• IUPAC Name: (2S,3R)-2-amino-N-[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1R)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]-3-hydroxybutanamide
• SMILES: CC(C)CC1C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCCC(C(=O)NC(C(=O)NC(C(=O)N1)CC2=CC=CC=C2)CCN)NC(=O)C(CCN)NC(=O)C(C(C)O)N)C(C)O)CCN)CCN
• InChI Key: PYHYGIPVYYRJHU-QWDNBKTCSA-N
• Boiling Point: 1456.2ºC at 760 mmHg
• Flash Point: 834.5ºC
• Density: 1.32g/cm³
• Appearance: solid
• Exact Mass: 962.56600

Case Study

Polymyxin B Nonapeptide as Outer Membrane Permeabilizer for Synergistic Antimicrobial Combinations

Khazandi, Manouchehr, et al. Frontiers in microbiology 10 (2019): 837.

Polymyxin B nonapeptide (PMBN) acts as a non-antibacterial outer membrane permeabilizer that sensitizes multidrug-resistant Gram-negative pathogens to robenidine, expanding the antimicrobial spectrum of robenidine for treating human and veterinary infections, including canine otitis externa.
Assay Protocol: Broth microdilution and checkerboard assays were used to determine minimum inhibitory concentrations (MIC), fractional inhibitory concentration indices (FICI), and dose reduction indices (DRI) against E. coli, P. aeruginosa, K. pneumoniae, and Acinetobacter spp. Time-kill kinetics and cytotoxicity in mammalian cell lines were also evaluated.
Performance Evaluation: PMBN alone showed no antibacterial activity against most Gram-negative strains but exerted strong synergism (FICI ≤ 0.5) with robenidine. This combination increased robenidine DRI by 8-256-fold and restored activity against multidrug-resistant isolates. PMBN exhibited low cytotoxicity (IC50 >32 μg/mL) in HaCaT, HEK 293, and MDCK cells. The synergistic pair provides a safe, potent strategy to combat resistant Gram-negative pathogens while supporting antimicrobial stewardship.

Polymyxin B Nonapeptide as Outer Membrane Permeabilizer to Convert Pleuromutilins to Broad-Spectrum Antibiotics

Luo, Xinyu, et al. Available at SSRN 5165726. 2025.

Polymyxin B nonapeptide (PMBN) serves as a non-bactericidal outer membrane permeabilizer that synergizes with novel pleuromutilin derivative 15b, extending its activity from Gram-positive-only to cover multidrug-resistant Gram-negative pathogens such as Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae.
Assay Protocol: Checkerboard microdilution was used to calculate fractional inhibitory concentration indices (FICI). Time-kill kinetics, spontaneous resistance frequency, and serial passage resistance development were tested. In vivo efficacy was evaluated in Galleria mellonella infection models.
Performance Evaluation: At 8 μg/mL, PMBN drove strong synergy (FICI < 0.1) with 15b, lowering MICs against Gram-negatives by up to 128-fold. The combination suppressed spontaneous resistance to <1.7×10^-9 and delayed resistance emergence better than valnemulin/PMBN. It achieved 60% survival in E. coli-infected G. mellonella with favorable safety. PMBN enables pleuromutilin repurposing as broad-spectrum agents while reducing polymyxin-related resistance.