Delving into the Latest Updates on Acorafloxacin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Acorafloxacin (USAN), Acorafloxacin Hydrochloride, Avarofloxacin

+ [4]

Target

Bacterial DNA gyrase x Top II x Topoisomerase IV

Mechanism

Bacterial DNA gyrase inhibitors, Top II inhibitors(Topoisomerase II inhibitors), Topoisomerase IV inhibitors

+ [1]

Therapeutic Areas

Infectious DiseasesRespiratory DiseasesSkin and Musculoskeletal Diseases

Active Indication

Community-acquired bacterial pneumoniaComplicated skin and skin structure infection

Inactive Indication

Complicated skin and soft tissue infection

Originator Organization

Janssen Global Services LLC

Active Organization

Johnson & Johnson Pharmaceutical Research & Development LLC

Inactive Organization

Furiex Pharmaceuticals, Inc.

Janssen Global Services LLCJanssen, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H23F2N3O4

InChIKeyVMKVDAAFMQKZJS-LFIBNONCSA-N

CAS Registry878592-87-1

Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such asStaphylococcus aureus,Pseudomonas aeruginosa,Streptococcus pneumoniaeand several of theEnterobacteriaceae. However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.

04 May 2022·Expert Review of Anti-infective TherapyQ2 · MEDICINE

Anti-MRSA quinolones for acute bacterial skin and skin structure infection: a systematic review and meta-analysis of randomized controlled trials

Q2 · MEDICINE

Review

Author: Chao, Chien-Ming ; Lin, Wei-Ting ; Weng, Teng-Song ; Chen, Yu-Hung ; Lai, Chih-Cheng

OBJECTSThis study compared the clinical efficacy and safety of anti-methicillin-resistant Staphylococcus aureus (MRSA) quinolones for treating acute bacterial skin and skin structure infections (ABSSSIs).METHODSPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to 21 July 2021. RCTs comparing the clinical efficacy and safety of anti-MRSA quinolones with other antibiotics for treating adult patients with ABSSSIs were included.RESULTSSix RCTs were included. A total of 1,264 and 1,307 participants received the anti-MRSA quinolone-based study group and the control group. In the study group receiving anti-MRSA quinolone-based treatment, 935, 246, and 83 patients received delafloxacin, levonadifloxacin, and acorafloxacin, respectively. No significant difference was observed in the clinical cure rate at test of cure between the study and control groups (OR, 1.08; 95% CI, 0.91-1.29; I² = 0%). In patients with MRSA-associated ABSSSIs, the clinical cure rate (OR, 1.09; 95% CI, 0.71-1.65; I² = 0%) and microbiological response rate (OR, 1.24; 95% CI, 0.48-3.21; I² = 0%) of anti-MRSA quinolones were similar to those of other antibiotics.CONCLUSIONSThe efficacy of anti-MRSA quinolone-based treatment is comparable to that of other anti-MRSA antibiotics for treating ABSSSIs.

24 Jun 2021·Journal of Medicinal ChemistryQ1 · MEDICINE

Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-b]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens

Q1 · MEDICINE

Article

Author: Meng, Xin ; Xue, Yaru ; Wang, Ting ; Pan, Wei ; Luo, Cheng ; Xu, Heng ; Zhang, Shuhua ; Kong, Qidi ; Guo, Bin ; Yang, Yushe

Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-b]indole derivatives represented by GP-1 demonstrated excellent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria but were limited by hERG inhibition and poor pharmacokinetics profile. To improve their drug-like properties, we designed a series of novel pyrimido[4,5-b]indole derivatives based on the tricyclic scaffold of GP-1 and the C-7 moiety of acorafloxacin. These efforts have culminated in the discovery of a promising compound 18r with reduced hERG liability and an improved PK profile. Compound 18r exhibited superior broad-spectrum in vitro antibacterial activity compared to GP-1, including a variety of clinical multidrug G^- pathogens, especially Acinetobacter baumannii, and the in vivo efficacy was also demonstrated in a neutropenic mouse thigh model of infection with multidrug-resistant A. baumannii.

100 Deals associated with Acorafloxacin

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External Link

KEGG	Wiki	ATC	Drug Bank
D10435	Acorafloxacin	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Complicated skin and skin structure infection	Phase 2	US	Furiex Pharmaceuticals, Inc.	01 Jun 2010
Community-acquired bacterial pneumonia	Phase 1	HU	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Community-acquired bacterial pneumonia	Phase 1	DE	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Community-acquired bacterial pneumonia	Phase 1	US	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Community-acquired bacterial pneumonia	Preclinical	CA	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Community-acquired bacterial pneumonia	Preclinical	PL	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Community-acquired bacterial pneumonia	Preclinical	CO	Furiex Pharmaceuticals, Inc.	01 Oct 2010
Pneumonia	Preclinical	-	Janssen Global Services LLC	-
Skin and skin structure infections	Preclinical	-	Janssen Global Services LLC	-
Complicated skin and soft tissue infection	Discovery	US	Furiex Pharmaceuticals, Inc.	-