A5003079010- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Antibiotics Pharmacokinetics and Efficacy
- Pharmaceutical studies and practices
- Treatment of Major Depression
- Alzheimer's disease research and treatments
- Bacterial biofilms and quorum sensing
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Steroid Chemistry and Biochemistry
- Pneumonia and Respiratory Infections
- Chemical Synthesis and Reactions
- Chemical Reaction Mechanisms
- Pharmacology and Obesity Treatment
- Stress Responses and Cortisol
- RNA modifications and cancer
- Mast cells and histamine
- Private Equity and Venture Capital
- Phenothiazines and Benzothiazines Synthesis and Activities
- Attention Deficit Hyperactivity Disorder
Entasis Therapeutics (United States)
2017-2021
Michigan Technological University
2018
AstraZeneca (United States)
2000-2016
Arnold Ventures
2015
Auckland City Hospital
2014
University of Florida
2014
First Pavlov State Medical University of St. Petersburg
2014
Sarasota University
2014
University of South Florida
2014
AstraZeneca (United Kingdom)
2000-2007
Fragment-based lead generation has led to the discovery of a novel series cyclic amidine-based inhibitors β-secretase (BACE-1). Initial fragment hits with an isocytosine core having millimolar potency were identified via NMR affinity screening. Structure-guided evolution these fragments using X-ray crystallography together determination surface plasmon resonance and functional enzyme inhibition assays afforded micromolar inhibitors. Similarity searching around identification related...
Cerebral deposition of amyloid β-protein (Aβ) is believed to play a key role in the pathogenesis Alzheimer's disease. Because Aβ produced from processing precursor (APP) by β- and γ-secretases, these enzymes are considered important therapeutic targets for identification drugs treat Unlike β-secretase, which monomeric aspartyl protease, γ-secretase activity resides as part membrane-bound, high molecular weight, macromolecular complex. Pepstatin L685458 among several structural classes...
The global emergence of antibiotic resistance, especially in Gram-negative bacteria, is an urgent threat to public health. Discovery novel classes antibiotics with activity against these pathogens has been impeded by a fundamental lack understanding the molecular drivers underlying small molecule uptake. Although it well-known that outer membrane porins represent main route entry for small, hydrophilic molecules across cell envelope, structure–permeation relationship porin passage yet be...
Meant to be an authoritative guide for psychiatrists and others interested in understanding applying ketamine psychedelic psychotherapy (KPP), this paper focuses on its pharmacology, phenomenology, clinical applications.Ketamine is a dissociative anesthetic widely used by physicians veterinarians the United States.In addition properties, also has multitude of other psychological pharmacological which include analgesic, sedative, neuroprotective, anxiolytic, antidepressant, stimulant,...
To identify new agents for the treatment of multi-drug-resistant Pseudomonas aeruginosa, we focused on siderophore-conjugated monocarbams. This class monocyclic β-lactams are stable to metallo-β-lactamases and have excellent P. aeruginosa activities due their ability exploit iron uptake machinery Gram-negative bacteria. Our medicinal chemistry plan identifying a molecule with optimal potency physical properties activity in vivo efficacy. Modifications monocarbam linker, siderophore, oxime...
A main challenge in the development of new agents for treatment Pseudomonas aeruginosa infections is identification chemotypes that efficiently penetrate cell envelope and are not susceptible to established resistance mechanisms. Siderophore-conjugated monocarbams attractive because their ability hijack bacteria's iron uptake machinery transport into periplasm inherent stability metallo-β-lactamases. Through SAR we identified a number modifications scaffold afforded active anti-P. with good...
A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds H3R functional assay. Exemplar compound 6s demonstrated a profile against panel 144 secondary pharmacological receptors, with activity at only σ2 (62% 10 μM). Compound free-plasma exposures above IC50 (∼50×) brain-to-plasma ratio ∼3 following intravenous...
The high-molecular mass penicillin-binding proteins (PBPs) are the essential targets of β-lactam classes antibacterial drugs. In Gram-negative pathogen Escherichia coli, these include PBP1a, PBP1b, PBP2, and PBP3. Techniques that enable facile measurement potency inhibition valuable for understanding structure–activity relationships in programs aimed at discovering new antibiotics to combat drug-resistant infections. Continuous fluorescence anisotropy-based assays soluble constructs PBP3...
The 1,3-dithiane-based dM-Dmoc group was studied for the protection of amino groups. Protection achieved under mild conditions aliphatic amines, and highly reactive less arylamines. Moderate to excellent yields were obtained. Deprotection performed by oxidation followed treating with a weak base. good excellent. new protecting offers different dimension orthogonality in reference commonly used groups terms deprotection conditions. It is expected allow collection transformations be carried...
A novel, ultrahigh-throughput, fluorescence anisotropy-based assay was developed and used to screen a 1.4-million-sample library for compounds that compete with adenosine triphosphate (ATP) binding Escherichia coli tRNA(Ile) lysidine synthetase (TilS), an essential, conserved, ATP-dependent, tRNA-modifying enzyme of bacterial pathogens. TilS modifies cytidine base in the anticodon loop Ile2 tRNA by attaching lysine, thereby altering codon recognition CAU from AUG (methionine) AUA...
Purpose – To explain and analyze SEC charges settlement with Kohlberg Kravis Roberts & Co. (“KKR”) related to misallocation of broken deal expenses. Design/methodology/approach Provides background, including other similar enforcement actions in relation private equity hedge funds; explains the regulatory violations KKR’s allocation methodology disclosure; draws lessons makes recommendations for firms concerning need compliance disclosure reviews benefits remediation cooperation. Findings...