| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary mechanism of action of Pexiganan is believed to be the disruption of microbial cytoplasmic membranes, leading to rapid cell death. It does not act on a specific molecular target like conventional antibiotics but rather interacts with the lipid components of the bacterial membrane. [1]
Pexiganan disrupts bacterial cytoplasmic membranes via electrostatic interactions with negatively charged phospholipids, leading to rapid cell lysis. It lacks specific molecular targets (e.g., enzymes/receptors), and no IC50/Ki/EC50 values for single targets are reported. [1][2][3][4] |
|---|---|
| ln Vitro |
The primary mechanism of action of Pexiganan is believed to be the disruption of microbial cytoplasmic membranes, leading to rapid cell death. It does not act on a specific molecular target like conventional antibiotics but rather interacts with the lipid components of the bacterial membrane. [1]
Pexiganan exhibited broad-spectrum antibacterial activity in vitro against a wide range of Gram-positive and Gram-negative bacteria commonly associated with skin and soft tissue infections, including isolates from diabetic foot ulcers. It was effective against both aerobic and anaerobic organisms. [1] Activity was demonstrated against organisms such as Staphylococcus aureus (including methicillin-resistant strains - MRSA), Staphylococcus epidermidis, Streptococcus pyogenes, Enterococcus faecalis (including vancomycin-resistant strains - VRE), Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species. [1] The minimum inhibitory concentrations (MICs) for most susceptible organisms were generally in the range of 16 to 32 µg/mL. [1] Its bactericidal activity was rapid. [1] Pexiganan exhibited broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens. MICs for clinical isolates were: E. coli (4–16 µg/mL), P. aeruginosa (8–32 µg/mL), S. aureus (4–16 µg/mL), Enterococcus spp. (8–32 µg/mL), and H. pylori (2–8 µg/mL; MIC₉₀ = 8 µg/mL). Bactericidal effects (≥3 log₁₀ CFU reduction within 1–4 hours at 4×MIC) were observed against E. coli, S. aureus, and H. pylori. Activity was reduced in acidic conditions (pH 5.5) or with high divalent cations (e.g., 10 mM Mg²⁺), but minimally affected by 50% human serum (≤2-fold MIC increase). [2][3] Pexiganan (128 µg/mL) showed low cytotoxicity to human gastric epithelial cells (GES-1) after 24 hours (cell viability >80% via MTT assay). [3] |
| ln Vivo |
In a mouse H. pylori infection model, oral pexiganan (20 mg/kg twice daily for 7 days) reduced gastric bacterial load by 2 log₁₀ CFU/g. Nanoparticle-formulated pexiganan (PNPs) enhanced efficacy (3.5 log₁₀ reduction). [3]
In a rat endotoxic shock model (LPS + D-galactosamine), intravenous pexiganan (1 mg/kg) increased survival to 67% (vs. 0% controls) and reduced plasma TNF-α by 75%. Synergy with ceftriaxone (10 mg/kg) yielded 100% survival. [4] Topical application of a 1% Pexiganan cream demonstrated efficacy in Phase II clinical trials for treating mild diabetic foot infections, showing comparable clinical success rates (85-90%) to oral ofloxacin (85%). [1] Efficacy was observed against infections involving both Gram-positive and Gram-negative pathogens, including Pseudomonas aeruginosa. [1] |
| Cell Assay |
Cell Assay:
Antibacterial activity: MICs were determined using broth microdilution per CLSI guidelines. Bacteria were incubated with serial pexiganan dilutions (0.25–128 µg/mL) in cation-adjusted Mueller-Hinton broth (Gram-positives/negatives) or Brucella broth + 5% FBS (H. pylori). Plates were incubated at 35°C for 16–24 hours (48 hours for H. pylori). MIC was defined as the lowest concentration inhibiting visible growth.
Time-kill kinetics: Bacteria at ~10⁶ CFU/mL were exposed to pexiganan (1–4×MIC). Aliquots were removed at intervals (0–24 hours), serially diluted, plated on agar, and counted after incubation. Cytotoxicity (GES-1 cells): Cells were seeded in 96-well plates, incubated with pexiganan (4–128 µg/mL) for 24 hours, then treated with MTT reagent. Formazan crystals were solubilized, and absorbance measured at 570 nm. Viability was calculated relative to untreated controls. [2][3] |
| Animal Protocol |
H. pylori infection model: Female C57BL/6 mice (6–8 weeks) were inoculated orally with H. pylori SS1 (3 doses over 5 days). After 4 weeks, infected mice received oral pexiganan (20 mg/kg in saline) twice daily for 7 days. Controls received saline. Mice were euthanized 3 days post-treatment; stomachs homogenized for CFU counting.
Endotoxic shock model: Male Sprague-Dawley rats (200–250 g) received intraperitoneal LPS (200 µg/kg) + D-galactosamine (700 mg/kg). One hour later, intravenous pexiganan (1 mg/kg in saline) was administered alone or with ceftriaxone (10 mg/kg). Survival was monitored for 24 hours; blood was collected at 1.5 hours for TNF-α ELISA. [3][4] |
| ADME/Pharmacokinetics |
Topical application of a 1% Pexiganan cream demonstrated efficacy in Phase II clinical trials for treating mild diabetic foot infections, showing comparable clinical success rates (85-90%) to oral ofloxacin (85%). [1]
Efficacy was observed against infections involving both Gram-positive and Gram-negative pathogens, including Pseudomonas aeruginosa. [1] Topical 1% cream caused mild application-site reactions (burning, erythema) at rates similar to vehicle control. No systemic toxicity, nephrotoxicity, or ototoxicity was observed clinically. In vitro, cytotoxicity to human fibroblasts was minimal at antibacterial concentrations. [1][3] Pexiganan (128 µg/mL) showed no hemolytic activity against human erythrocytes after 1 hour. [2] |
| Toxicity/Toxicokinetics |
Topical Pexiganan (1% cream) was generally well-tolerated in Phase II clinical trials. [1]
The most common adverse events were mild, transient application site reactions (e.g., burning, pain, erythema, rash), occurring at a similar frequency to the vehicle cream control. [1] No systemic toxicity attributable to the drug was observed. [1] No evidence of ototoxicity or nephrotoxicity was found. [1] Plasma protein binding and detailed toxicokinetic studies were not reported, likely due to negligible systemic absorption. [1] In vitro studies showed minimal cytotoxicity to human fibroblasts at concentrations effective against bacteria. [1] Preclinical studies indicated a lack of mutagenic potential. [1] |
| References | |
| Additional Infomation |
Pexiganan is a synthetic 22-residue magainin analog developed for topical treatment of infected diabetic foot ulcers. Its membrane-disrupting mechanism may reduce resistance development. Phase II trials demonstrated efficacy against mild infections, including Pseudomonas-positive wounds. [1][2]
Nanoparticle encapsulation (PNPs) improved pexiganan's stability and in vivo anti-H. pylori efficacy. [3] In endotoxic shock models, pexiganan suppressed TNF-α and synergized with β-lactams, suggesting immunomodulatory effects. [4] Pexiganan acetate (MSI-78) is a synthetic cationic antimicrobial peptide analogue based on the magainin peptides found in the skin of the African clawed frog (Xenopus laevis). [1] It was developed as a topical antimicrobial agent, specifically for the treatment of infected diabetic foot ulcers. [1] Its proposed mechanism is physical disruption of bacterial cell membranes, making the development of resistance less likely compared to conventional antibiotics targeting specific biochemical pathways. [1] Phase II clinical trials demonstrated its efficacy was comparable to oral ofloxacin in achieving clinical cure or improvement of mild diabetic foot infections. [1] Its favorable safety profile and negligible systemic absorption make it a promising agent for localized treatment, potentially avoiding systemic antibiotic use and associated resistance development or side effects. [1] |
| Molecular Formula |
C122H210N32O22.XC2H4O2
|
|---|---|
| Molecular Weight |
2477.17 (free base)
|
| Exact Mass |
2535.65
|
| Elemental Analysis |
C, 58.70; H, 8.50; N, 17.67; O, 15.13
|
| CAS # |
172820-23-4
|
| Related CAS # |
172820-23-4 (acetate); 147664-63-9
|
| PubChem CID |
16129735
|
| Sequence |
H-Gly-Ile-Gly-Lys-Phe-Leu-Lys-Lys-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Lys-Ile-Leu-Lys-Lys-NH2.CH3CO2H; Gly-Ile-Gly-Lys-Phe-Leu-Lys-Lys-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Lys-Ile-Leu-Lys-Lys-NH2;
glycyl-L-isoleucyl-glycyl-L-lysyl-L-phenylalanyl-L-leucyl-L-lysyl-L-lysyl-L-alanyl-L-lysyl-L-lysyl-L-phenylalanyl-glycyl-L-lysyl-L-alanyl-L-phenylalanyl-L-valyl-L-lysyl-L-isoleucyl-L-leucyl-L-lysyl-L-lysinamide acetic acid
|
| SequenceShortening |
GIGKFLKKAKKFGKAFVKILKK; GIGKFLKKAKKFGKAFVKILKK-NH2
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1
|
| Hydrogen Bond Donor Count |
32
|
| Hydrogen Bond Acceptor Count |
32
|
| Rotatable Bond Count |
94
|
| Heavy Atom Count |
176
|
| Complexity |
4940
|
| Defined Atom Stereocenter Count |
20
|
| SMILES |
CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N)NC(=O)CN
|
| InChi Key |
DNTVNGJSMLPWQF-CVJDLQKLSA-N
|
| InChi Code |
InChI=1S/C122H210N32O22/c1-13-78(10)103(153-99(155)71-132)121(175)135-73-101(157)139-86(49-25-34-58-125)110(164)152-97(69-82-43-19-15-20-44-82)119(173)150-94(66-75(4)5)117(171)145-90(53-29-38-62-129)113(167)142-87(50-26-35-59-126)109(163)137-79(11)105(159)141-88(51-27-36-60-127)112(166)143-91(54-30-39-63-130)114(168)151-96(68-81-41-17-14-18-42-81)107(161)134-72-100(156)138-85(48-24-33-57-124)108(162)136-80(12)106(160)147-98(70-83-45-21-16-22-46-83)120(174)154-102(77(8)9)122(176)146-92(55-31-40-64-131)115(169)148-95(67-76(6)7)118(172)149-93(65-74(2)3)116(170)144-89(52-28-37-61-128)111(165)140-84(104(133)158)47-23-32-56-123/h14-22,41-46,74-80,84-98,102-103H,13,23-40,47-73,123-132H2,1-12H3,(H2,133,158)(H,134,161)(H,135,175)(H,136,162)(H,137,163)(H,138,156)(H,139,157)(H,140,165)(H,141,159)(H,142,167)(H,143,166)(H,144,170)(H,145,171)(H,146,176)(H,147,160)(H,148,169)(H,149,172)(H,150,173)(H,151,168)(H,152,164)(H,153,155)(H,154,174)/t78-,79-,80-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,102-,103-/m0/s1
|
| Chemical Name |
(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S,3S)-2-[(2-aminoacetyl)amino]-3-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]hexanoyl]amino]propanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]hexanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]hexanamide
|
| Synonyms |
MSI 78; Locilex; 63S35FF5KS; MSI-78; 172820-23-4; Cytolex; Pexiganan Acetate; Pexiganan (acetate); SCHEMBL487091;
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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