Delving into the Latest Updates on Blasticidin analog P10 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target-

Action-

Mechanism-

Therapeutic Areas

Infectious Diseases

Active Indication-

Inactive Indication

Bacterial Infections

Originator Organization

National Institutes of Health

Active Organization-

Inactive Organization

National Institutes of Health

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

ABSTRACT The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all S. aureus isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of norA , suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics.

100 Deals associated with Blasticidin analog P10

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