| 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 |
In a phase II clinical trial, topical application of 1% Pexiganan cream showed efficacy in treating mild diabetic foot infections, with a clinical success rate (85-90%) comparable to that of oral ofloxacin (85%). [1]
The cream was effective against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. [1] The incidence of mild site reactions (burning, erythema) caused by topical application of 1% cream was similar to that in the excipient control group. No systemic toxicity, nephrotoxicity, or ototoxicity was observed clinically. In vitro studies showed that the cream had very low cytotoxicity to human fibroblasts at antibacterial concentrations. [1][3] Pexiganan (128 µg/mL) did not show hemolytic activity against human erythrocytes after 1 hour. [2] |
| Toxicity/Toxicokinetics |
In a phase II clinical trial, topical application of 1% Pexiganan cream was well tolerated. [1] The most common adverse reactions were mild, transient site reactions (e.g., burning, pain, erythema, rash), occurring at a frequency similar to that in the excipient cream control group. [1] No systemic toxicity associated with the drug was observed. [1] No evidence of ototoxicity or nephrotoxicity was found. [1] Plasma protein binding and detailed toxicokinetic studies were not reported due to negligible systemic absorption. [1] In vitro studies showed that the drug had very low cytotoxicity to human fibroblasts at concentrations effective against bacteria. [1] Preclinical studies indicated that the drug lacked mutagenicity. [1]
|
| References | |
| Additional Infomation |
Pexiganan is a synthetic 22-peptide amino acid residue magainin analog developed for the topical treatment of infectious diabetic foot ulcers. Its cell membrane disruption mechanism may help reduce the development of resistance. Phase II clinical trials showed that it was effective against mild infections, including Pseudomonas aeruginosa positive wounds. [1][2] Nanoparticle encapsulation (PNPs) improved the stability of Pexiganan and its in vivo efficacy against Helicobacter pylori. [3] In an endotoxin shock model, Pexiganan inhibited the expression of TNF-α and had a synergistic effect with β-lactam antibiotics, suggesting an immunomodulatory effect. [4] Pexiganan acetate (MSI-78) is a synthetic cationic antimicrobial peptide analog based on magainin peptides found in the skin of Xenopus laevis. [1] It was initially developed as a topical antimicrobial agent specifically for the treatment of infectious diabetic foot ulcers. [1]
Its mechanism of action is believed to be the physical disruption of bacterial cell membranes, which makes it less likely to develop resistance compared to traditional antibiotics that target specific biochemical pathways. [1] Phase II clinical trials showed that its efficacy in curing or improving mild diabetic foot infections was comparable to that of oral ofloxacin. [1] Its good safety profile and negligible systemic absorption make it a promising topical treatment that could potentially avoid the systemic use of antibiotics and their associated resistance 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
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|---|---|
| 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00563394
Conditions:Diabetic Foot UlcersLink: https://clinicaltrials.gov/ct2/show/NCT00563433
Conditions:Diabetic Foot UlcersProducts are for research use only; We do not sell to patients
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