Delving into the Latest Updates on Pexiganan Acetate with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Locilex, Pexiganan, Pexiganan acetate (USAN)

+ [2]

Target-

Action

enhancers

Mechanism

Cell membrane permeability enhancers

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [1]

Active Indication

Diabetic Foot

Inactive Indication

Complicated skin and soft tissue infectionDiabetic foot infectionDiabetic foot ulcer+ [2]

Originator Organization

Genaera Corp.

Active Organization

Genaera Corp.

Inactive Organization

Abeona Therapeutics, Inc.

Dipexium Pharmaceuticals, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC122H210N32O22.C2H4O2

InChIKeyZYMCXUWEZQKVIO-IJAHCEAPSA-N

CAS Registry172820-23-4

Sequence Code 44584

Source: *****

Author: Shahrour, H ; Santos, S.G. ; Ribeiro, A.R. ; Martínez-de-Tejada, G. ; Ribeiro, A R ; Monteiro, C. ; Costa, F ; Coelho, J. ; Coelho, J ; Silva, V. ; Costa, B ; Martins, M C L ; Martins, M.C.L. ; Santos, S G ; Costa, B. ; Costa, F. ; Silva, V ; Martínez-de-Tejada, G ; Costa, N A ; Costa, N.A. ; Monteiro, C ; Shahrour, H.

Infection is one of the major issues associated with the failure of orthopedic devices, mainly due to implant bacterial colonization, biofilm formation, and associated antibiotic resistance. Antimicrobial peptides (AMP) are a promising alternative to conventional antibiotics given their broad-spectrum of activity, low propensity to induce bacterial resistance, and ability to modulate host immune responses. Dhvar5 (LLLFLLKKRKKRKY) and MSI78 (GIGKFLKKAKKFGKAFVKILKK) are two AMP with broad-spectrum activity against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), one of the most problematic etiologic agents in Orthopedic Devices-Related Infections (ODRI). This work aims to evaluate the bactericidal, immunomodulatory and osteogenic potential of Dhvar5- and MSI78-coated titanium surfaces (AMP-Ti). Two AMP-Ti surfaces were successfully obtained by grafting Dhvar5 (0.8 ± 0.1 µM/mm²) or MSI78 (0.5 ± 0.3 µM/mm²) onto titanium substrates through a polydopamine layer. Both AMP-Ti were bactericidal against MRSA, eradicating bacteria upon contact for 6 h in a culture medium supplemented with human plasma proteins. The AMP-Ti immunomodulatory potential was evaluated using human primary macrophages, by assessing surfaces capacity to induce pro-/anti-inflammatory (M1/M2) markers and cytokines. While in naïve conditions both AMP-Ti surfaces slightly promoted the M2 marker CD163, in response to LPS and IFN-γ (simulating a bacterial infection), both AMP increased the M1 marker CCR7 and enhanced macrophage secretion of pro-inflammatory IL-6 and TNF-α cytokines, particularly for Ti-MSI78 surfaces. Additionally, both AMP-Ti surfaces were cytocompatible and promoted osteoblastic cell differentiation. This proof-of-concept study demonstrated the high potential of Dhvar5- and MSI78-Ti as antimicrobial coatings for ODRI prevention. STATEMENT OF SIGNIFICANCE: This study investigates the bactericidal effects of the antimicrobial peptides Dhvar5 and MSI78, immobilized on titanium (Ti) surfaces through a polydopamine coating, aiming at the prevention of Orthopedic-Device Related Infections (ODRIs). The developed coatings displayed MRSA-sterilizing activity, while revealing an immunomodulatory potential towards macrophages and promoting osteoblastic cell differentiation. This strategy allows a quick and easy immobilization of high quantities of AMP, unlike most other approaches, thus favoring its clinical translation.

17 Dec 2024·Langmuir

Assessment of Linear and Cyclic Peptides’ Immobilization onto Cross-Linked, Poly(vinyl alcohol)/Cellulose Nanocrystal Nanofibers Electrospun over Quartz Crystal Microbalances with Dissipation Sensors

Article

Author: Murthy, N. Sanjeeva ; Teixeira, Marta A. ; Felgueiras, Helena P. ; Ferreira, Diana P.

Immobilization of peptides onto nanofiber dressings holds significant potential for chronic wound treatment. However, it is necessary to understand the adsorptive capacity of the produced substrates and the binding affinity of the peptides to determine the interface success. This study aims at exploring for the first time the influence of electrospun poly(vinyl alcohol)-based nanofibers on the adsorption of a cyclic peptide, Tiger 17, and of a linear peptide, Pexiganan, using quartz crystal microbalance with dissipation monitoring (QCM-D). PVA fibers reinforced with 0, 10, and 20% w/v cellulose nanocrystals (CNC) were electrospun directly onto QCM-D sensors and, posteriorly, cross-linked by glutaraldehyde vapor. Adsorption levels of Pexiganan were the highest (∼7348 ng/cm²) on C80/20 PVA/CNC electrospun fibers, while the time to achieve equilibrium was the longest (∼235 min). In contrast, the adsorption mass with cyclic Tiger 17 was the highest (∼3428 ng/cm²) on C100/0 PVA, reaching equilibrium after nearly 123 min. In sequential deposition, the combination Tiger 17 + Pexiganan on C100/0 fibers attained the highest number of bound peptide molecules, with ∼55% of Tiger 17 and ∼45% of Pexiganan. Elastic shear modulus data on this peptide sequence, over the C80/20 electrospun mats, reported 220 and 249 kPa for each peptide, respectively, indicating the formation of stable bonds with the surface. The results contributed to the understanding of the immobilization of linear and cyclic peptides, never studied in combination, and their mutual influence on polymeric substrates for engineering potential wound treatment strategies.

10 Oct 2024·The Journal of Physical Chemistry B

Understanding Antimicrobial Peptide Synergy: Differential Binding Interactions and Their Impact on Membrane Integrity

Article

Author: Yoon, Jeseong ; Jo, Youngbeom ; Shin, Seokmin

Research on antimicrobial peptides (AMPs) has been conducted as a solution to overcome antibiotic resistance. In particular, the synergistic effect that appears when two or more AMPs are used in combination has been observed. To find an effective synergistic combination, it is necessary to understand the underlying mechanism. However, a consistent explanation for this phenomenon has not yet been provided due to limitations in experimentally determining or predicting the structure of the heteroaggregates formed by the interactions between different AMPs and the interaction of the aggregate surface with the lipid membrane surface. In this study, we conducted molecular dynamics simulations for two heterogeneous aggregates of melittin-indolicidin and pexiganan-indolicidin to observe their structures in the solution phase and their interactions with the lipid membrane. We aimed to determine how the surfaces of these aggregates interact with the lipid membrane. Due to the different amino acid residue sequence characteristics of melittin and pexiganan, we found that when the two AMPs bind to indolicidin, they form aggregates with completely different structural characteristics. Accordingly, the sequence characteristics of pexiganan, which exhibits a relatively unstable structure compared to melittin in aqueous solution or on lipid membranes, allow for a more stable interaction with the lipid membrane when forming aggregates with indolicidin, effectively inhibiting the integrity of the lipid membranes. We also found that the amino acid residues forming the surface of the AMP aggregate show differential binding strengths to different lipid species forming the lipid membrane, thereby disrupting the membrane in a way that weakens its integrity. Through this, we provided insight into the basic principle of how the synergistic effect of AMPs occurs.

100 Deals associated with Pexiganan Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
D05448	-	-	DB16293

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic Foot	Phase 3	-	Genaera Corp.	-
Impetigo	Preclinical	United States	Genaera Corp.	-
Diabetic foot infection	Discovery	United States	Dipexium Pharmaceuticals, Inc.	01 Jun 2014
Diabetic foot ulcer	Discovery	United States	Abeona Therapeutics, Inc.	01 Aug 1994
Diabetic ulcer	Discovery	United States	Abeona Therapeutics, Inc.	01 Aug 1994
Complicated skin and soft tissue infection	Discovery	United States	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01590758 (OneStep-1, CTgov)	Phase 3	Diabetic foot infection	189	Standard wound care+Topical pexiganan cream 0.8% (Topical Pexiganan Cream 0.8%)	unoaigmodh(qgxrevqtol) = pcxfhrenwj ktfoiqmwtt (fgdrggfcla, nfbdzrujxu - cofgmarukb) View more	-	14 Jun 2017
				Topical placebo cream (Topical Placebo Control)	unoaigmodh(qgxrevqtol) = sytjupajdx ktfoiqmwtt (fgdrggfcla, xzbddhwrjp - fspgyizhvi) View more
NCT01594762 (OneStep-2, CTgov)	Phase 3	Diabetic foot infection	200	Standard wound care+Topical pexiganan cream 0.8% (Topical Pexiganan Cream 0.8%)	obcmnettxi(kpjranxaoa) = vhrnpfjzyt axamfqccjm (gisoqmfugo, ltcwxhcntd - zxpvihkgkx) View more	-	14 Jun 2017
				Topical placebo cream (Topical Placebo Control)	obcmnettxi(kpjranxaoa) = rcdlfsgwll axamfqccjm (gisoqmfugo, endtrjdsge - sfvxwidyjt) View more

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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