培西加南(Pexiganan Acetate) - 在研适应症：糖尿病足_专利_临床

概要

基本信息

药物类型

合成多肽

别名

Locilex、Pexiganan、Pexiganan acetate (USAN)

+ [2]

靶点-

作用方式

增强剂

作用机制

细胞膜通透性增强剂

治疗领域

神经系统疾病心血管疾病内分泌与代谢疾病+ [1]

在研适应症

糖尿病足

非在研适应症

复杂的皮肤和软组织感染糖尿病足感染糖尿病足溃疡+ [2]

原研机构

Genaera Corp.

在研机构

Genaera Corp.

非在研机构

Abeona Therapeutics, Inc.

Dipexium Pharmaceuticals, Inc.

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C122H210N32O22.C2H4O2

InChIKeyZYMCXUWEZQKVIO-IJAHCEAPSA-N

CAS号172820-23-4

Sequence Code 44584

来源: *****

关联

5

项与培西加南相关的临床试验

IRCT20190924044863N1

/ Completed临床1期IIT

Evaluate the safety, side effects and maximum tolerable dose of topical application of Antimicrobial Peptides: Pexiganan (MSI-78), Tilapia piscidin 4 (TP4), Melittin, Nisin-A and Omiganan (MX-226) on the skin of healthy volunteers to the treatment of Skin and Soft Tissue Infections.

开始日期2020-07-22

申办/合作机构

Mashhad University of Medical Sciences

NCT01594762

/ Completed临床3期

A Randomized, Double-Blind, Multicenter, Superiority, Placebo-Controlled Phase 3 Study of Pexiganan Cream 0.8% Applied Twice Daily for 14 Days in the Treatment of Adults With Mild Infections of Diabetic Foot Ulcers

The purpose of this study is to establish the clinical superiority and the safety of topical pexiganan cream 0.8% plus standard local wound care as compared to placebo cream plus standard local wound care, in the treatment of mildly infected diabetic foot ulcers.

开始日期2014-06-01

申办/合作机构

Dipexium Pharmaceuticals, Inc.

NCT01590758

/ Completed临床3期

A Randomized, Double-Blind, Multicenter, Superiority, Placebo-Controlled Phase 3 Study of Pexiganan Cream 0.8% Applied Twice Daily for 14 Days in the Treatment of Adults With Mild Infections of Diabetic Foot Ulcers

The purpose of this study is to establish the clinical superiority and the safety of topical pexiganan cream 0.8% plus standard local wound care, as compared to placebo cream plus standard local wound care, in the treatment of mildly infected diabetic foot ulcers.

开始日期2014-06-01

申办/合作机构

Dipexium Pharmaceuticals, Inc.

100 项与培西加南相关的临床结果

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100 项与培西加南相关的转化医学

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100 项与培西加南相关的专利（医药）

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147

项与培西加南相关的文献（医药）

2025-01-01·Acta Biomaterialia

Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic

Article

作者: 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.

2024-12-17·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

作者: 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.

2024-10-10·The Journal of Physical Chemistry B

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

Article

作者: 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 项与培西加南相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05448	-	-	DB16293

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
糖尿病足	临床3期	-	Genaera Corp.	-
脓疱疮	临床前	美国	Genaera Corp.	-
糖尿病足感染	药物发现	美国	Dipexium Pharmaceuticals, Inc.	2014-06-01
糖尿病足溃疡	药物发现	美国	Abeona Therapeutics, Inc.	1994-08-01
糖尿病溃疡	药物发现	美国	Abeona Therapeutics, Inc.	1994-08-01
复杂的皮肤和软组织感染	药物发现	美国	-	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01590758 (OneStep-1, CTgov)	临床3期	糖尿病足感染	189	Standard wound care+Topical pexiganan cream 0.8% (Topical Pexiganan Cream 0.8%)	積積築膚遞遞鹹淵鬱願(衊網繭鏇範積築淵襯範) = 選壓齋範觸糧製遞製積醖選觸鹽鑰選艱夢築簾 (鹹積廠淵廠鹹鏇衊壓獵, 鹹範糧繭餘襯顧構築構 ~ 鑰選壓艱蓋鏇選願構蓋) 更多	-	2017-06-14
				Topical placebo cream (Topical Placebo Control)	積積築膚遞遞鹹淵鬱願(衊網繭鏇範積築淵襯範) = 窪憲網餘願繭襯壓構糧醖選觸鹽鑰選艱夢築簾 (鹹積廠淵廠鹹鏇衊壓獵, 艱鹽廠願鹹網齋繭願鏇 ~ 窪壓夢遞憲願鬱憲範鏇) 更多
NCT01594762 (OneStep-2, CTgov)	临床3期	糖尿病足感染	200	Standard wound care+Topical pexiganan cream 0.8% (Topical Pexiganan Cream 0.8%)	艱衊簾築糧齋築鑰獵醖(鹽餘膚遞衊襯築衊製積) = 窪窪壓齋餘艱範壓鑰齋範範願築顧築壓製築糧 (餘築遞襯顧糧獵範積糧, 糧鑰廠壓積製鑰積構遞 ~ 糧選鹹衊鹽觸構顧積齋) 更多	-	2017-06-14
				Topical placebo cream (Topical Placebo Control)	艱衊簾築糧齋築鑰獵醖(鹽餘膚遞衊襯築衊製積) = 網窪糧顧餘簾範築選範範範願築顧築壓製築糧 (餘築遞襯顧糧獵範積糧, 選選鹹壓範製憲遞鏇齋 ~ 觸齋簾構憲壓窪願構醖) 更多