A5059505755- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Synthetic Organic Chemistry Methods
- DNA and Nucleic Acid Chemistry
- Asymmetric Synthesis and Catalysis
- Mechanisms of cancer metastasis
- Hydrogen Storage and Materials
- Carbon dioxide utilization in catalysis
- Immune Cell Function and Interaction
- Mosquito-borne diseases and control
- Chemical Synthesis and Reactions
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- Viral Infections and Vectors
- Chemical Synthesis and Analysis
- Organic Chemistry Cycloaddition Reactions
- PI3K/AKT/mTOR signaling in cancer
- Herpesvirus Infections and Treatments
- Malaria Research and Control
- Synthesis and Catalytic Reactions
- RNA modifications and cancer
- HIV Research and Treatment
- Metalloenzymes and iron-sulfur proteins
- Histone Deacetylase Inhibitors Research
- Viral Infections and Outbreaks Research
University College London
2019-2024
University of York
2003-2010
Abstract The tetrasubstituted naphthalene diimide compound QN-302 binds to G-quadruplex (G4) DNA structures. It shows high potency in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits the transcription of cancer-related genes these PDAC animal models. is currently Phase 1a clinical evaluation as an anticancer drug. A study structure–activity relationships two related analogues (CM03 SOP1247) reported here. These have been probed using comparisons transcriptional profiles from...
Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists be made available. Broad-spectrum antivirals drugs with the potential inhibit infection by viruses from different groups families, which may deployed during outbreaks when diagnostics, directly acting not While pathogen-directed approaches generally effective...
Targeting of genomic quadruplexes is an approach to treating complex human cancers. We describe a series tetra-substituted naphthalene diimide (ND) derivatives with phenyl substituent directly attached the ND core. The lead compound (SOP1812) has 10 times superior cellular and in vivo activity compared previous compounds nanomolar binding quadruplexes. pharmacological properties SOP1812 indicate good bioavailability, which consistent xenograft genetic models for pancreatic cancer....
Among CD4+ T cells, helper 17 (Th17) cells are particularly susceptible to HIV-1 infection and depleted from mucosal sites, which causes damage the gut barrier, resulting in a microbial translocation-induced systemic inflammation, hallmark of disease progression. Furthermore, proportion latently infected Th17 persist long term gastrointestinal lymphatic tract where low-level transcription is observed. This residual viremia contributes chronic immune activation. Thus, key players HIV...
The metastasis suppressor protein NME1 is an evolutionarily conserved and multifunctional enzyme that plays important role in suppressing the invasion of tumour cells. nucleoside diphosphate kinase (NDPK) activity well recognized balancing intracellular pools nucleotide diphosphates triphosphates to regulate cytoskeletal rearrangement cell motility, endocytosis, trafficking, metastasis. In addition, was found function as a protein-histidine kinase, 3′-5′ exonuclease geranyl/farnesyl...
Interactions are reported of three representative naphthalenediimide derivatives with quadruplex targets, from the promoter region telomerase (hTERT) gene, a human telomeric DNA quadruplex, and RNA (TERRA). Thermal melting studies showed that these compounds strongly stabilize quadruplexes, weak stabilization duplex DNA. Binding by surface plasmon resonance fluorescence spectroscopy found bind to quadruplexes nanomolar equilibrium dissociation constants. Plausible topologies for complexes...
The first systematic study of the cis and trans stereoselectivity in m-CPBA epoxidation N-protected cyclic allylic amines has been completed. Mono-N-protected systems gave epoxides with stereochemistry (amides are better directors than sulfonamides or carbamates) whereas di-N-protected trans-epoxides (TsNBoc protection complete stereoselectivity).
ABSTRACT Members of the Flaviviridae family constitute a severe risk to human health. Whilst effective drugs have been developed against hepacivirus HCV, no antiviral therapy is currently available for any other viruses, including flaviviruses dengue (DENV), West Nile and Zika viruses. The RNA-dependent RNA polymerase (RdRp) responsible viral replication represents an excellent therapeutic target with homologue found in mammals. identification compounds targeting RdRp active area research....
Human cytomegalovirus (HCMV) is major pathogen of nonimmunocompetent individuals that remains in need new therapeutic options. Here, we identify a potent antiviral compound (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid [DIDS]), its mechanism action, and the chemical properties required for activity. In doing so, data argue cysteine-reactive compounds could have capacity to be developed anti-HCMV Importantly, show entry DIDS-resistant virus became independent heparan sulfate proteoglycans...
Abstract Among CD4+ T-cells, T helper 17 (Th17) cells are particularly susceptible to HIV-1 infection and depleted from mucosal sites, which causes damage the gut barrier resulting in microbial translocation-induced systemic inflammation, a hallmark of disease progression. Furthermore, proportion latently infected Th17 persist long-term gastro-intestinal lymphatic tract, where low-level transcription is observed. This residual viremia contributes chronic immune activation. Thus, key players...
Abstract For see ChemInform in Full Text.
Abstract The compound SOP1812, a tetra-substituted naphthalene diimide derivative has been previously disclosed to have single-digit nM anti-proliferative activity in panel of human pancreatic ductal adenocarcinoma (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also significant anti-tumor the MIA-PACA2 xenograft model for PDAC as well more demanding KPC model. We now report that this shows three patient-derived (PDX) models PDAC. One is from primary tumor at...