Delving into the Latest Updates on Radezolid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Radezolid (USAN/INN), Radezolid Hydrochloride

+ [7]

Target

23S rRNA x 50S subunit

Mechanism

23S rRNA modulators(23S Ribosomal RNA modulators), 50S subunit inhibitors(50S ribosomal subunit inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

MRSA - Methicillin resistant Staphylococcus aureus infectionVancomycin-resistant enterococcal infection

Inactive Indication

AbscessCommunity Acquired PneumoniaComplicated skin and skin structure infection+ [2]

Originator Organization

Melinta Therapeutics, Inc.

Active Organization

Melinta Subsidiary Corp.

Inactive Organization

Melinta Therapeutics, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H23FN6O3

InChIKeyBTTNOGHPGJANSW-IBGZPJMESA-N

CAS Registry869884-78-6

Gram-positive bacterial infections are among the most serious diseases related with high mortality rates and huge healthcare costs especially with the rise of antibiotic-resistant strains that limits treatment options. Thus, development of new antibiotics combating these multi-drug resistant bacteria is crucial. Oxazolidinone antibiotics are the only totally synthetic group of antibiotics that showed activity against multi-drug resistant Gram positive bacteria including MRSA because of their unique mechanism of action in targeting protein synthesis. This group include approved marketed members (tedizolid, linezolid and contezolid) or those under development (delpazlolid, radezolid and sutezolid). Due to the significant impact of this class, larger number of analytical methods were required to meet the needs of both clinical and industrial studies. Analyzing these drugs either alone or with other antimicrobial agents commonly used in ICU, in the presence of pharmaceutical or endogenous biological interferences, or in the presence of matrix impurities as metabolites and degradation products poses a big analytical challenge. This review highlights current analytical approaches published in the last decade (2012-2022) that dealt with the determination of these drugs in different matrices and discusses their advantages and disadvantages. Various techniques have been described for their determination including chromatographic, spectroscopic, capillary electrophoretic and electroanalytical methods. The review comprises six sections (one for each drug) with their related tables that depict critical figures of merit and some experimental conditions for the reviewed methods. Furthermore, future perspectives about the analytical methodologies that can be developed in the near future for determination of these drugs are suggested.

01 Jan 2023·Frontiers in microbiology

Antibacterial and anti-biofilm activity of radezolid against Staphylococcus aureus clinical isolates from China.

Article

Author: Deng, Qiwen ; Yu, Zhijian ; Wei, Ying ; Deng, Xiangbing ; Wang, Cong ; Wen, Zewen ; Cao, Xinyi ; Li, Guiqiu ; Xiong, Yanpeng ; Bao, Chai

Although the potent antibacterial ability of radezolid against Staphylococcus aureus has been widely reported worldwide, its antibacterial and anti-biofilm activity against the S. aureus clinical isolates from China remains elusive. In this study, the minimum inhibitory concentration (MIC) of radezolid was determined in S. aureus clinical isolates from China using the agar dilution method, and the relationship between radezolid susceptibility and ST distribution was also investigated. The anti-biofilm activity of radezolid against S. aureus was determined by a crystal violet assay and compared with that of linezolid and contezolid. The quantitative proteomics of S. aureus treated with radezolid was analyzed, and the genetic mutations in radezolid-induced resistant S. aureus were determined by whole-genome sequencing. The dynamic changes in transcriptional expression levels of several biofilm-related genes were analyzed by quantitative RT-PCR. Our data showed that radezolid MIC ranged from ≤0.125 to 0.5 mg/L, which was almost 1/4 × MIC of linezolid against S. aureus, indicating the greater antibacterial activity of radezolid than linezolid. The S. aureus clinical isolates with radezolid MICs of 0.5 mg/L were most widely distributed in ST239 of MRSA and ST7 of MSSA. Moreover, the more robust anti-biofilm activity of radezolid with subinhibitory concentrations (1/8 × MIC and 1/16 × MIC) was demonstrated against S. aureus when compared with that of contezolid and linezolid. Genetic mutations were found in glmS, 23S rRNA, and DUF1542 domain-containing protein in radezolid-induced resistant S. aureus selected by in vitro induction of drug exposure. Quantitative proteomic analysis of S. aureus indicated that the global expression of some biofilm-related and virulence-related proteins was downregulated. Quantitative RT-PCR further confirmed that the expressions of some downregulated biofilm-related proteins, including sdrD, carA, sraP, hlgC, sasG, spa, sspP, fnbA, and oatA, were decreased after 12 h and 24 h of exposure to radezolid. Conclusively, radezolid shows robust antibacterial and anti-biofilm activity against S. aureus clinical isolates from China when compared with contezolid and linezolid.

01 Dec 2022·European Journal of Medicinal Chemistry

1,2,3-Triazole-containing hybrids with potential antibacterial activity against ESKAPE pathogens

Review

Author: Wang, Jun ; Yan, Heng ; Liu, Bao-Shan ; Liu, Kai ; Shi, Yu-Min ; Deng, Cui

ESKAPE pathogens, as priority 1 and 2 pathogens, are prevalent infectious agents associated with high morbidity and mortality. ESKAPE can cause broad-spectrum diseases with increasing tendency of resistance acquisition to antibiotics and have enhanced the urge for the development of alternate therapeutics. 1,2,3-Triazole, a highly privileged moiety for the discovery of novel drugs, not only can act as a linker to tether different pharmacophores, but also can serve as a pharmacophore. Notably, several 1,2,3-triazole-containing hybrids which are exemplified by cefatrizine, radezolid and tazobactam have already approved as antibiotics to treat infections caused by various organisms including ESKAPE pathogens and their drug-resistant forms, revealing that 1,2,3-triazole-containing hybrids are useful prototypes for clinical deployment in the control of bacterial infections. The purpose of the present review article is to provide an emphasis on the current scenario (2018-2022) of 1,2,3-triazole-containing hybrids with potential antibacterial activity against ESKAPE pathogens to facilitate further rational design of more effective candidates.

100 Deals associated with Radezolid

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External Link

KEGG	Wiki	ATC	Drug Bank
D09369	Radezolid	-	DB12339

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	US	Melinta Subsidiary Corp.	05 Jul 2008
Vancomycin-resistant enterococcal infection	Preclinical	US	Melinta Subsidiary Corp.	05 Jul 2008
Abscess	Discovery	US	Melinta Therapeutics, Inc.	01 Dec 2007
Complicated skin and skin structure infection	Discovery	US	Melinta Therapeutics, Inc.	01 Dec 2007
Staphylococcal Skin Infections	Discovery	US	Melinta Therapeutics, Inc.	01 Dec 2007
Streptococcal Infections	Discovery	US	Melinta Therapeutics, Inc.	01 Dec 2007
Community Acquired Pneumonia	Discovery	CA	Melinta Therapeutics, Inc.	01 Oct 2007
Community Acquired Pneumonia	Discovery	US	Melinta Therapeutics, Inc.	01 Oct 2007
Community Acquired Pneumonia	Discovery	RU	Melinta Therapeutics, Inc.	01 Oct 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00640926 (CTgov)	Phase 2	Community Acquired Pneumonia	158	Radezolid (Radezolid 300 mg PO Daily (QD))	ntosyhvauo(hkokndwrbp) = ibpmqrrqsm jagddfaepk (alppjusmik, pqbztumfmq - rrnopcbxrk) View more	-	04 Feb 2010
				Radezolid (Radezolid 450 mg PO Daily (QD))	ntosyhvauo(hkokndwrbp) = ugfvzjyfgy jagddfaepk (alppjusmik, xllfdftptu - dtkxzragpc) View more
NCT00646958 (CTgov)	Phase 2	Complicated skin and skin structure infection \| Abscess \| Streptococcal Infections \| Staphylococcal Skin Infections	150	Radezolid (Radezolid QD)	vqdqarysus(cfpjysavgq) = uhwedoqwge riqmuxbxqe (klezlpmawo, envuqovdar - cqcgmjwdjp) View more	-	26 Jun 2009
				Radezolid (Radezolid BID)	vqdqarysus(cfpjysavgq) = csqamlbunh riqmuxbxqe (klezlpmawo, vbdzmrrglt - ikgrxqdzqy) View more