A5076759117- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Pharmacogenetics and Drug Metabolism
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Receptor Mechanisms and Signaling
- Microbial Natural Products and Biosynthesis
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Genetics, Bioinformatics, and Biomedical Research
- Biotechnology and Related Fields
- Adenosine and Purinergic Signaling
- Veterinary Orthopedics and Neurology
- Biomedical Text Mining and Ontologies
- RNA and protein synthesis mechanisms
- Disaster Management and Resilience
- Veterinary Oncology Research
- Synthesis and biological activity
- Chemical Synthesis and Analysis
- Advanced Drug Delivery Systems
- Advanced Radiotherapy Techniques
- Glycosylation and Glycoproteins Research
- HIV/AIDS Research and Interventions
Liverpool Hospital
2018-2025
Cardiff and Vale University Health Board
2020-2023
BioScientia (Poland)
2022
Exscien (United States)
2022
Bioscientifica (United Kingdom)
2021
University of Dundee
2008-2018
Research Complex at Harwell
2018
Park Avenue Dermatology
2016
University of New Mexico
2008
Pfizer (United Kingdom)
2001-2008
Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range chemically diverse non-nucleoside inhibitors (NNIs) have shown single pocket in which the bind and details inhibitor-protein interactions. To delineate structural requirements for an effective inhibitor, we determined three closely related NNIs vary widely their potencies. RT two very potent inhibitors, MKC-442 TNK-651, at 2.55 angstroms resolution complement our previous analysis complex less HEPT. These reveal...
The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting polymerase active site upon binding nearby pocket. Despite being potent and generally low toxicity, their clinical use has been limited rapid selection resistant populations. 2.65-Å resolution structure complex between RT bis(heteroaryl)piperazine (BHAP) NNI,...
Fragment-based drug discovery is a validated approach for the of candidates. However, weak affinity fragment compounds requires highly sensitive biophysical techniques, such as nuclear magnetic resonance (NMR) or X-ray crystallography, to identify hits. Thus advantages screening small libraries are partly offset by high cost analyses. Here we present method biosensor-based using surface plasmon (SPR). In order reduce false positive detection rate novel data analysis that incorporates...
A recent viewpoint article (Improving the plausibility of success with inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that standard definition ligand efficiency (LE) is mathematically invalid. In this viewpoint, we address criticism and show categorically LE valid. other metrics such as lipophilic (LLE) can be useful during multiparameter optimization challenge faced by medicinal chemists.
Sole reliance on one drug, Praziquantel, for treatment and control of schistosomiasis raises concerns about development widespread resistance, prompting renewed interest in the discovery new anthelmintics. To discover leads we designed an automated label-free, high content-based, throughput screen (HTS) to assess drug-induced effects vitro cultured larvae (schistosomula) using bright-field imaging. Automatic image analysis Bayesian prediction models define morphological damage, hit/non-hit...
G-protein coupled receptors (GPCRs) are a class of drug targets primary importance. However, receptor assays based on measurement either ligand displacement or downstream functional responses, rather than direct observation binding. Issues allosteric modulation, probe dependence, and selectivity create challenges in selecting suitable formats. Therefore, method that directly measures GPCR-ligand interactions, independent binding site, probe, signaling pathway would be useful orthogonal...
Abstract Stereotactic radiosurgery ( SRS ) is a procedure that delivers single large radiation dose to well‐defined target. Here, we describe frameless technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with primary tumour by imaging or histopathology underwent were retrospectively reviewed. Frameless was used successfully treat tumours 51 variety head sizes and shapes. Tumours included 38 meningiomas, 4 pituitary tumours, trigeminal nerve 3 gliomas, 1...
Two analogues of the nonnucleoside inhibitor HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible commonly found drug-resistance mutation Tyr181Cys. Compound TNK-6123 had a thiocyclohexyl group more flexibility in adapting mutated drug-binding site. GCA-186 additional 3',5'-dimethyl aimed at forming close contacts with conserved residue Trp229. Both compounds showed ∼30-fold greater inhibitory effect than Tyr181Cys mutant virus as well...