Delving into the Latest Updates on Omiganan with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Omiganan pentachloride, Omiganan pentahydrochloride, Omiganan pentahydrochloride (USAN)

+ [7]

Target-

Mechanism

Cell membrane permeability enhancers

Therapeutic Areas

Eye Diseases

Active Indication

Bullous keratopathy

Inactive Indication

Acne VulgarisBacteremiaCondylomata Acuminata+ [5]

Originator Organization

Carrus Technologies, Inc.

Active Organization-

Inactive Organization

Cutanea Life Sciences, Inc.Global Gaming Technologies Corp.

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC90H128ClN27O12

InChIKeyXZVPZZJCWDNELR-NLRWEPRHSA-N

CAS Registry269062-93-3

View All Structures (2)

Sequence Code 116133

Source: *****

Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.

01 Nov 2023·Asian Journal of Pharmaceutical Sciences

An infection-microenvironment-targeted and responsive peptide-drug nanosystem for sepsis emergency by suppressing infection and inflammation

Article

Author: Gai, Yongkang ; Fu, Daan ; Ye, Zhilan ; Liu, Xingxin ; Chang, Bingcheng ; Chen, Xu ; Liu, Jia ; He, Wei ; Yang, Chang

Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation. Nevertheless, current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens. Omiganan, an antimicrobial peptide, has shown promise for neutralizing endotoxins and eliminating diverse pathogens. However, its clinical application is hindered by safety and stability concerns. Herein, we present a nanoscale drug delivery system (Omi-hyd-Dex@HA NPs) that selectively targets infectious microenvironments (IMEs) and responds to specific stimuli for efficient intervention in sepsis. The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid (HA). The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes, but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase. The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation. In multiple tissue infection and sepsis animal models, Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction, thereby preventing subsequent fatal complications and significantly improving survival outcomes. The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.

01 Apr 2023·Amino Acids

Rational design of stapled antimicrobial peptides

Review

Author: Zhu, YouZhuo ; Liu, HongYu ; Zheng, Heng ; You, YuHao

The global increase in antimicrobial drug resistance has dramatically reduced the effectiveness of traditional antibiotics. Structurally diverse antibiotics are urgently needed to combat multiple-resistant bacterial infections. As part of innate immunity, antimicrobial peptides have been recognized as the most promising candidates because they comprise diverse sequences and mechanisms of action and have a relatively low induction rate of resistance. However, because of their low chemical stability, susceptibility to proteases, and high hemolytic effect, their usage is subject to many restrictions. Chemical modifications such as D-amino acid substitution, cyclization, and unnatural amino acid modification have been used to improve the stability of antimicrobial peptides for decades. Among them, a side-chain covalent bridge modification, the so-called stapled peptide, has attracted much attention. The stapled side-chain bridge stabilizes the secondary structure, induces protease resistance, and increases cell penetration and biological activity. Recent progress in computer-aided drug design and artificial intelligence methods has also been used in the design of stapled antimicrobial peptides and has led to the successful discovery of many prospective peptides. This article reviews the possible structure-activity relationships of stapled antimicrobial peptides, the physicochemical properties that influence their activity (such as net charge, hydrophobicity, helicity, and dipole moment), and computer-aided methods of stapled peptide design. Antimicrobial peptides under clinical trial: Pexiganan (NCT01594762, 2012-05-07). Omiganan (NCT02576847, 2015-10-13).

100 Deals associated with Omiganan

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External Link

KEGG	Wiki	ATC	Drug Bank
D05262	-	-	DB06610

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dermatitis, Atopic	Phase 2	NL	Cutanea Life Sciences, Inc.	25 Nov 2016
Condylomata Acuminata	Phase 2	NL	Cutanea Life Sciences, Inc.	06 Apr 2016
Vulvar intraepithelial neoplasia	Phase 2	NL	Cutanea Life Sciences, Inc.	21 Nov 2015
Rosacea	Phase 2	AU	Cutanea Life Sciences, Inc.	13 Aug 2015
Propionibacterium Acnes Infection	Phase 2	-	Global Gaming Technologies Corp.	01 Oct 2000
Bacteremia	Phase 2	US	Global Gaming Technologies Corp.	01 Sep 2000
Fungemia	Phase 2	US	Global Gaming Technologies Corp.	01 Sep 2000
Acne Vulgaris	Phase 2	US	Global Gaming Technologies Corp.	-
Bullous keratopathy	Phase 2	JP	-	-
Acne Vulgaris	Discovery	US	Global Gaming Technologies Corp.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02576847 (CTgov)	Phase 3	Rosacea	307	Omiganan	vgpgcaqozp(ohloaldnff) = avyokfwwhp guhvyyzbks (qbzxydjvaa, dbtfcyxxsp - lmvvthuvzo) View more	-	06 Jul 2022