Delving into the Latest Updates on (R)-ZG197 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CLPP

Mechanism

CLPP agonists(caseinolytic mitochondrial matrix peptidase proteolytic subunit agonists)

Therapeutic Areas

Infectious Diseases

Active Indication

Bacterial Infections

Inactive Indication-

Originator Organization

University of Chinese Academy of Sciences

Active Organization

University of Chinese Academy of Sciences

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC28H35F3N4O3

InChIKeyBAZGDIOJCKGDHH-RHDWJPPYSA-N

CAS Registry2999672-72-7

Methicillin-resistant Staphylococcus aureus is a ubiquitous pathogen, posing a serious threat to human health worldwide. Thus, there is a high demand for antibiotics with distinct targets. Caseinolytic protease P (ClpP) is a promising target for combating staphylococcal infections; however, selectively activating S. aureus ClpP (SaClpP) rather than Homo sapiens ClpP (HsClpP) remains challenging. Herein, we rationally design and identify ZG297 by structure-based strategy. It binds and activates SaClpP instead of HsClpP. This is due to differentiated ligand binding attributed to crossed "tyrosine/histidine" amino acid pairs. ZG297 substantially inhibits the growth of a broad panel of S. aureus strains in vitro, outperforming the selective (R)-ZG197 agonist. ZG297 also functions as a potent antibiotic against multidrug-resistant S. aureus infections in Galleria mellonella larvae, zebrafish, murine skin, and thigh infection models. Collectively, we demonstrate that ZG297 is a safer and more potent antistaphylococcal agent than acyldepsipeptide 4 and (R)-ZG197.

100 Deals associated with (R)-ZG197

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