Amy M. Flattery

Discovery of Broad-Spectrum Herpes Antiviral Oxazolidinone Amide Derivatives and Their Structure–Activity Relationships

Michael A. Plotkin, Marc A. Labroli, Jeffrey W. Schubert, Anthony W. Shaw et autres

Herpesvirus infections are ubiquitous, with over 95% of the adult population infected by at least one strain. While most of these infections resolve without treatment in healthy individuals, they can cause significant morbidity and mortality in immunocompromised, stem cell, or organ transplant …

us (code pays fourni par la source)

Rapid Evolution of a Fragment-like Molecule to Pan-Metallo-Beta-Lactamase Inhibitors: Initial Leads toward Clinical Candidates

Mihirbaran Mandal, Li Xiao, Weidong Pan, Giovanna Scapin et autres

With the emergence and rapid spreading of NDM-1 and existence of clinically relevant VIM-1 and IMP-1, discovery of pan inhibitors targeting metallo-beta-lactamases (MBLs) became critical in our battle against bacterial infection. Concurrent with our fragment and high-throughput screenings, we performed a knowledge-based …

us (code pays fourni par la source)

Nocathiacin, Thiazomycin, and Polar Analogs Are Highly Effective Agents against Toxigenic Clostridioides difficile

Sheo Bux Singh, Lynn Miesel, Susanne Krämer, Libo Xu et autres

Clostridioides difficile is a commensal Gram-positive gut bacterium that causes C. difficile -associated diarrhea. Currently available antibacterial therapeutic treatment options are effective except for the repeated recurrences significantly burdening the health care system and causing mortality. The development of new therapeutic modalities …

us (code pays fourni par la source)

Ibrexafungerp: An orally active β-1,3-glucan synthesis inhibitor

James M. Apgar, Robert R. Wilkening, Dann L. Parker, Dongfang Meng et autres

us (code pays fourni par la source)

MK-5204: An orally active β-1,3-glucan synthesis inhibitor

James M. Apgar, Robert R. Wilkening, Dann L. Parker, Dongfang Meng et autres

us (code pays fourni par la source)

Use of Translational Pharmacokinetic/Pharmacodynamic Infection Models To Understand the Impact of Neutropenia on the Efficacy of Tedizolid Phosphate

Jianying Xiao, Charles Gill, Lianzhu Liang, Jenny X. Liu et autres

(MSSA) strain (ATCC 29213). The antistaphylococcal effect of doses ranging from 1 to 150 mg/kg of body weight tedizolid (once daily) or linezolid (twice daily) was determined at 24, 48, and 72 h after initiating treatment. In IC mice, stasis was achieved …

us (code pays fourni par la source)

Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting

Hao Wang, Paul A. Mann, Li Xiao, Charles Gill et autres

us, de (code pays fourni par la source)

Can We Make Small Molecules Lean? Optimization of a Highly Lipophilic TarO Inhibitor

Mihirbaran Mandal, Zheng Tan, Christina B. Madsen-Duggan, Alexei V. Buevich et autres

We describe our optimization efforts to improve the physicochemical properties, solubility, and off-target profile of 1, an inhibitor of TarO, an early stage enzyme in the biosynthetic pathway for wall teichoic acid (WTA) synthesis. Compound 1 displayed a TarO IC 50 of …

us (code pays fourni par la source)

Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis

Stephen A. Wring, Ryan Randolph, Seonghee Park, George K. Abruzzo et autres

ABSTRACT SCY-078 (MK-3118) is a novel, semisynthetic derivative of enfumafungin and represents the first compound of the triterpene class of antifungals. SCY-078 exhibits potent inhibition of β-(1,3)- d -glucan synthesis, an essential cell wall component of many pathogenic fungi, including Candida spp. …

us (code pays fourni par la source)

Use of translational PKPD infection models to understand impact of neutropenia on efficacy of tedizolid phosphate

Jianying Xiao, Charles Gill, Lianzhu Liang, Jenny X. Liu et autres

Tedizolid phosphate (TZD), an oxazolidinone antibiotic, has been approved in the United States, Europe, and other countries to treat adults with acute bacterial skin and skin structure infections (ABSSSI). Translational PKPD studies in neutropenic mouse infection models demonstrated improved potency and PKPD …

us (code pays fourni par la source)

Disease Progression and Resolution in Rodent Models of Clostridium difficile Infection and Impact of Antitoxin Antibodies and Vancomycin

Peter A. Warn, Pia A. Thommes, Abdul Sattar, David F. Corbett et autres

Clostridium difficile causes infections of the colon in susceptible patients. Specifically, gut dysbiosis induced by treatment with broad-spectrum antibiotics facilitates germination of ingested C. difficile spores, expansion of vegetative cells, and production of symptom-causing toxins TcdA and TcdB. The current standard of …

gb, us (code pays fourni par la source)

TarO-specific inhibitors of wall teichoic acid biosynthesis restore β-lactam efficacy against methicillin-resistant staphylococci

Sang Ho Lee, Hao Wang, Marc A. Labroli, Sandra Koseoglu et autres

The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current β-lactam antibiotics and created an urgent need for new treatment options. We report an S. aureus phenotypic screening strategy involving chemical suppression of the growth inhibitory consequences …

us (code pays fourni par la source)