Delving into the Latest Updates on PZ-2891 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PANK1

Mechanism

PanK agonists(pantothenate kinase 1 agonists)

Therapeutic Areas

Nervous System DiseasesCongenital DisordersOther Diseases

Active Indication

Pantothenate Kinase-Associated Neurodegeneration

Inactive Indication-

Originator Organization

St. Jude Children's Research Hospital, Inc.

Active Organization

Nurix Therapeutics, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H23N5O

InChIKeyLGWDVWIZDPGCFG-UHFFFAOYSA-N

CAS Registry2170608-82-7

SummaryFungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies.

100 Deals associated with PZ-2891

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