A5027632767- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Plant-based Medicinal Research
- PI3K/AKT/mTOR signaling in cancer
- Nicotinic Acetylcholine Receptors Study
- Carbohydrate Chemistry and Synthesis
- Microbial Natural Products and Biosynthesis
- Alkaloids: synthesis and pharmacology
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Synthetic Organic Chemistry
- Organometallic Complex Synthesis and Catalysis
- X-ray Diffraction in Crystallography
- Chemical Reactions and Isotopes
- Organoboron and organosilicon chemistry
- RNA regulation and disease
- Eosinophilic Disorders and Syndromes
- Berberine and alkaloids research
- Mycobacterium research and diagnosis
- Synthesis and biological activity
- Crystallization and Solubility Studies
- Bioactive Compounds and Antitumor Agents
Imperial College London
2007
Cancer Society of New Zealand
2002
University of Auckland
2002
University of Bath
1993-2001
UCB Pharma (United Kingdom)
2001
University of Warwick
1992-1994
Abstract Therapies that enhance antitumor immunity have altered the natural history of many cancers. Consequently, leveraging nonoverlapping mechanisms to increase immunogenicity cancer cells remains a priority. Using novel enzymatic inhibitor RNA methyltransferase METTL3, we demonstrate global decrease in N6-methyladenosine (m6A) results double-stranded (dsRNA) formation and profound cell-intrinsic interferon response. Through unbiased CRISPR screens, establish dsRNA-sensing signaling are...
A novel class of orally active antimalarial 3,5-diaryl-2-aminopyridines has been identified from phenotypic whole cell high-throughput screening a commercially available SoftFocus kinase library. The compounds were evaluated in vitro for their antiplasmodial activity against K1 (chloroquine and drug-resistant strain) NF54 (chloroquine-susceptible as well cytotoxicity. Synthesis structure–activity studies number promising with selective activity. One these frontrunner compounds, 15, was...
A series of substituted angular benzophenazines were prepared using a new synthetic route via novel regiocontrolled condensation 1,2-naphthoquinones and 2,3-diaminobenzoic acids. The synthesis biological activity this 8,9-benzo[a]phenazine carboxamide systems are described. analogues evaluated against the H69 parental human small cell lung carcinoma line H69/LX4 resistant which overexpresses P-glycoprotein. Selected COR-L23 non COR-L23/R multidrug resistance protein. This potent cytotoxic...
Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) displays remarkable selectivity toward neuronal [125I]-α-bungarotoxin (αBgTX) binding sites that correspond to α7-type nAChR in brain. We have shown that, among number of selected norditerpenoid alkaloids, elatine (2) nudicauline (3) are equipotent with, or better than, MLA (1) brain [125I]-αBgTX sites, with IC50 values 6.1, 1.7, 7.6 nM, respectively. The...
The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on Biacore(™) T100 against and two selectivity targets. A sub-set of our library focus detailed follow-up analyses that included hit confirmation, affinity determination 24 confirmed, selective hits competition assays these with respect known ATP binding site inhibitor. In addition, functional activity...
Methyllycaconitine (MLA) is a competitive antagonist of nicotinic acetylcholine receptors, with remarkable preference for neuronal [ 125 I]αBgt binding sites. We have begun to investigate the structural basis its potency and subtype selectivity. MLA substituted norditerpenoid alkaloid linked 2‐(methylsuccinimido)benzoyl moiety. Hydrolysis ester bond in produce lycoctonine diminished affinity rat brain sites 2500‐fold abolished 3 H]nicotine muscle The voltage‐gated Na + channel activator...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPendant Alkenes Promote Cobalt−Cobalt Bond Cleavage in (Alkyne)(binap)tetracarbonyldicobalt(0) ComplexesSusan E. Gibson, Karina A. C. Kaufmann, Peter R. Haycock, Andrew J. P. White, David Hardick, and Matthew TozerView Author Information Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, U.K., Medivir UK Ltd., Chesterford Research Park, Little Chesterford, Essex C10 1XL, U.K. Cite this: Organometallics...
D. J. Hardick, W. Hutchinson, S. Trew and E. M. H. Wellington, Chem. Soc., Commun., 1991, 729 DOI: 10.1039/C39910000729
Two different asymmetric hydrogenation methodologies based on gaseous hydrogen at 1 atm pressure and transfer from the decomposition of formic acid, in presence a rhodium catalyst, have been used to prepare (S)-(−)-methylsuccinic acid enriched with deuterium isotope. NMR mass spectroscopic evidence indicates that complex labeling occurs. We interpret this pattern as result an equilibrium which exists between olefin catalyst-alkyl intermediate Wilkinson-type mechanism. This phenomenon has not...
Abstract Four (binap)(enyne)tetracarbonyldicobalt(0) complexes have been synthesised and their reactivity monitored by variable temperature 31 P NMR spectroscopy. Formation of (binap)dicarbonylhydridocobalt(−1) 12 occurred at temperatures between 35 55 °C, depending on the nature alkene alkyne components enyne. The structure was determined X‐ray crystallography, its presence under Pauson–Khand reaction conditions verified
Conference Article| August 01 1997 Structure-activity studies of bicyclic and tricyclic analogues methyllycaconitine ANDREW R. L. DAVIES; DAVIES aSchool Biology Biochemistry, University Bath, BA2 7AY, UK Search for other works by this author on: This Site PubMed Google Scholar DAVID J. HARDICK; HARDICK bSchool Pharmacy Pharmacology, IAN S. BLAGBROUGH; BLAGBROUGH BARRY V. POTTER; POTTER ADRIAN WOLSTENHOLME; WOLSTENHOLME SUSAN WONNACOTT Biochem Soc Trans (1997) 25 (3): 545S....
<div>Abstract<p>Therapies that enhance antitumor immunity have altered the natural history of many cancers. Consequently, leveraging nonoverlapping mechanisms to increase immunogenicity cancer cells remains a priority. Using novel enzymatic inhibitor RNA methyltransferase METTL3, we demonstrate global decrease in N6-methyladenosine (m6A) results double-stranded (dsRNA) formation and profound cell-intrinsic interferon response. Through unbiased CRISPR screens, establish...
<p>Gene expression changes + pathways</p>
<p>Proliferation + Apoptosis assays</p>
<p>METTL3 KD in B16 cell line</p>
<p>A20 lymphoma model data</p>