Ian H. Gilbert
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View article: Crystallographic characterisation and development of bi-substrate inhibitors of coronavirus nsp14 methyltransferase
Crystallographic characterisation and development of bi-substrate inhibitors of coronavirus nsp14 methyltransferase Open
SARS-CoV-2 non-structural protein 14 (nsp14) is essential for viral mRNA cap guanine-N7 methylation and represents a promising but underexplored antiviral target.
View article: Compounds Reducing Human Sperm Motility as Potential Nonhormonal Contraceptives Identified Using a High-Throughput Phenotypic Screening Platform
Compounds Reducing Human Sperm Motility as Potential Nonhormonal Contraceptives Identified Using a High-Throughput Phenotypic Screening Platform Open
In this article, we detail our latest findings toward developing a diversified series of potential nonhormonal contraceptive compounds using a phenotypic screening approach against human sperm. Phenotypic screening of nine compound librari…
View article: Target product profile and discovery and development path for novel cryptococcal disease treatments
Target product profile and discovery and development path for novel cryptococcal disease treatments Open
Cryptococcus neoformans and Cryptococcus gattii are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle-income countries, …
View article: Use of P450 Enzymes for Late-Stage Functionalization in Drug Discovery
Use of P450 Enzymes for Late-Stage Functionalization in Drug Discovery Open
Herein, we demonstrate the use of a commercially available enzymatic kit to achieve late-stage hydroxylation of biologically relevant compounds by using the PolyCYPs screening kit. A selection of promising biotransformations were scaled up…
View article: The Medical Need for Patients with Schistosomiasis
The Medical Need for Patients with Schistosomiasis Open
Schistosomiasis affects around 140 million people worldwide, with the highest impact on people living in low- or middle-income countries. Although the number of deaths due to schistosomiasis seems relatively low, there is a long-term healt…
View article: Crystallographic characterisation and development of bi-substrate inhibitors of coronavirus nsp14 methyltransferase
Crystallographic characterisation and development of bi-substrate inhibitors of coronavirus nsp14 methyltransferase Open
SARS-CoV-2 non-structural protein 14 (nsp14) is essential for viral mRNA cap guanine-N7 methylation and represents a promising but underexplored antiviral target. Herein we describe a structure-guided campaign based on a hit from a focusse…
View article: Small molecule inhibitors of the NorA multidrug efflux pump potentiate antibiotic activity by binding the outward-open conformation
Small molecule inhibitors of the NorA multidrug efflux pump potentiate antibiotic activity by binding the outward-open conformation Open
Antibiotic resistance is among the greatest threats of the modern era. Multidrug efflux pumps expel antibiotics from bacterial cells and present a particular challenge by conferring resistance to a broad range of antibiotic classes; howeve…
View article: Implementing and Evaluating an IoC-Driven Early Warning System for Enhanced Cybersecurity Resilience
Implementing and Evaluating an IoC-Driven Early Warning System for Enhanced Cybersecurity Resilience Open
In the contemporary digital landscape, organizations are increasingly confronted by sophisticated cyber threats that render traditional reactive security measures inadequate, particularly in the face of advanced persistent threats (APTs) a…
View article: Compounds reducing human sperm motility as potential non hormonal contraceptives identified using a high-throughput phenotypic screening platform
Compounds reducing human sperm motility as potential non hormonal contraceptives identified using a high-throughput phenotypic screening platform Open
In this article, we detail our latest findings towards developing diversified series of potential non-hormonal contraceptive compounds using a phenotypic screening approach against human sperm. Phenotypic screening of nine compound librari…
View article: Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining
Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining Open
Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- a…
View article: Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining
Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining Open
The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by i…
View article: <i>Cryptosporidium</i> lysyl-tRNA synthetase inhibitors define the interplay between solubility and permeability required to achieve efficacy
<i>Cryptosporidium</i> lysyl-tRNA synthetase inhibitors define the interplay between solubility and permeability required to achieve efficacy Open
Cryptosporidiosis is a diarrheal disease caused by infection with Cryptosporidium spp. parasites and is a leading cause of death in malnourished children worldwide. The only approved treatment, nitazoxanide, has limited efficacy in this at…
View article: FMOPhore for hotspot identification and efficient fragment-to-lead growth strategies
FMOPhore for hotspot identification and efficient fragment-to-lead growth strategies Open
Fragment based drug design (FBDD) is like a chess game in that a good or a bad move can dramatically influence the outcome. At the start of the design process, it is important to identify the key binding site residues (hotspots) that can h…
View article: Accurate prediction of dynamic protein–ligand binding using <scp><i>P‐score</i></scp> ranking
Accurate prediction of dynamic protein–ligand binding using <span><i>P‐score</i></span> ranking Open
Protein–ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, includin…
View article: Sperm Toolbox—A selection of small molecules to study human spermatozoa
Sperm Toolbox—A selection of small molecules to study human spermatozoa Open
Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either impro…
View article: Design of the Global Health chemical diversity library v2 for screening against infectious diseases
Design of the Global Health chemical diversity library v2 for screening against infectious diseases Open
There is a need for novel chemical matter for phenotypic and target-based screens to find starting points for drug discovery programmes in neglected infectious diseases and non-hormonal contraceptives that disproportionately affect Low- an…
View article: Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity
Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity Open
There is an urgent need for new tuberculosis (TB) treatments, with novel modes of action, to reduce the incidence/mortality of TB and to combat resistance to current treatments. Through both chemical and genetic methodologies, polyketide s…
View article: Accurate prediction of ligand binding for a flexible protein using P-score ranking.
Accurate prediction of ligand binding for a flexible protein using P-score ranking. Open
Protein ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, includin…
View article: Small-Molecule Antibiotic Drug Development: Need and Challenges
Small-Molecule Antibiotic Drug Development: Need and Challenges Open
The need for new antibiotics is urgent. Antimicrobial resistance is rising, although currently, many more people die from drug-sensitive bacterial infections. The continued evolution of drug resistance is inevitable, fueled by pathogen pop…
View article: Correction to “Bespoke Drug Discovery Training for Low-Middle Income Countries”
Correction to “Bespoke Drug Discovery Training for Low-Middle Income Countries” Open
[This corrects the article DOI: 10.1021/acsmedchemlett.3c00215.].
View article: Sperm Cell Painting: A Mechanism Driven Approach for Drug Discovery in Human Spermatozoa
Sperm Cell Painting: A Mechanism Driven Approach for Drug Discovery in Human Spermatozoa Open
We have adapted the cell painting assay developed by Carpenter and colleagues on cultured U2OS cells to human spermatozoa. In Sperm Cell Painting (SCP) we assemble an image-based quantitative fingerprint of the functional state of sperm. W…
View article: Safe and effective treatments are needed for cryptosporidiosis, a truly neglected tropical disease
Safe and effective treatments are needed for cryptosporidiosis, a truly neglected tropical disease Open
Cryptosporidiosis Therapeutics Advocacy Group: : Samuel L M Arnold, PhD, University of Washington School of Pharmacy; Beatriz Baragana, PhD, University of Dundee; Lynn Barrett, University of Washington; Frederick S Buckner, MD, University …
View article: Structure-Guided Design and Synthesis of a Pyridazinone Series of <i>Trypanosoma cruzi</i> Proteasome Inhibitors
Structure-Guided Design and Synthesis of a Pyridazinone Series of <i>Trypanosoma cruzi</i> Proteasome Inhibitors Open
There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral le…
View article: Bespoke Drug Discovery Training for Low-Middle Income Countries
Bespoke Drug Discovery Training for Low-Middle Income Countries Open
Working in drug discovery is difficult for many institutions due to the need for resources, funding, and in-country expertise. The Wellcome Centre for Anti-Infective Research (WCAIR) is responding to the unmet training needs for individual…
View article: Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static–Cidal Screening of Analogues
Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static–Cidal Screening of Analogues Open
While treatment options for human African trypanosomiasis (HAT) have improved significantly, there is still a need for new drugs with eradication now a realistic possibility. Here, we report the development of 2,4-diaminothiazoles that dem…
View article: Sperm Toolbox – A selection of small molecules to study human spermatozoa
Sperm Toolbox – A selection of small molecules to study human spermatozoa Open
Male contraceptive options and infertility treatments are limited. To help overcome these limitations we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profi…