A5033306158- Carbohydrate Chemistry and Synthesis
- DNA Repair Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- PARP inhibition in cancer therapy
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
- Cell Adhesion Molecules Research
- Trypanosoma species research and implications
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Enzyme Production and Characterization
- Enzyme Structure and Function
- Fluorine in Organic Chemistry
- Research on Leishmaniasis Studies
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- Glycogen Storage Diseases and Myoclonus
- Cancer Genomics and Diagnostics
- Synthesis and Biological Evaluation
UNSW Sydney
2023-2025
Children's Cancer Institute Australia
2023-2025
The University of Melbourne
2011-2024
Walter and Eliza Hall Institute of Medical Research
2012-2024
Alder Hey Children's Hospital
2021
University of Liverpool
2021
Monash University
2011-2019
Paediatric Integrated Cancer Service
2019
Commonwealth Scientific and Industrial Research Organisation
2019
Instituto Nacional do Câncer
2012
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSlow- and tight-binding inhibitors of the 85-kDa human phospholipase A2Ian P. Street, Hung Kuei Lin, France Laliberte, Farideh Ghomashchi, Zhaoyin Wang, Helene Perrier, Nathalie M. Tremblay, Zheng Huang, Philip K. Weech, Michael H. GelbCite this: Biochemistry 1993, 32, 23, 5935–5940Publication Date (Print):June 15, 1993Publication History Published online1 May 2002Published inissue 15 June...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUnequivocal demonstration of the involvement a glutamate residue as nucleophile in mechanism retaining glycosidaseStephen G. Withers, R. Antony J. Warren, Ian P. Street, Karen Rupitz, Julie B. Kempton, and Ruedi AebersoldCite this: Am. Chem. Soc. 1990, 112, 15, 5887–5889Publication Date (Print):July 1, 1990Publication History Published online1 May 2002Published inissue 1 July...
Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase mature body size. Here we show that the SOCS2-/- is dependent upon presence of endogenous hormone (GH) and treatment with exogenous GH induced mice lacking both SOCS2. This was reflected terms overall weight, bone lengths, weight internal organs tissues. A heightened response to also measured examining GH-responsive genes expressed liver after administration. To further understand link between...
Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30–50% increase mature body size. Here we show that the SOCS2–/– is dependent upon presence of endogenous hormone (GH) and treatment with exogenous GH induced mice lacking both SOCS2. This was reflected terms overall weight, bone lengths, weight internal organs tissues. A heightened response to also measured examining GH-responsive genes expressed liver after administration. To further understand link between...
Mechanism-based glycosidase inhibitors are of considerable use in studies enzyme mechanism, glycoprotein processing, and possibly therapeutically control sugar uptake. This paper describes a new general approach to mechanism-based inactivation glycosidases which involves trapping covalent glycosyl intermediate. is achieved by 2-deoxy-2-fluoro-D-glycosyl fluorides, for the rate hydrolysis fluoroglycosyl intermediate extremely slow, resulting accumulation Eleven different were tested with...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogen bonding and specificity. Fluorodeoxy sugars as probes of hydrogen in the glycogen phosphorylase-glucose complexIan P. Street, Charles R. Armstrong, Stephen G. WithersCite this: Biochemistry 1986, 25, 20, 6021–6027Publication Date (Print):October 7, 1986Publication History Published online1 May 2002Published inissue 7 October 1986https://pubs.acs.org/doi/10.1021/bi00368a028https://doi.org/10.1021/bi00368a028research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Deoxy-2-fluoroglucosides: a novel class of mechanism-based glucosidase inhibitorsStephen G. Withers, Ian P. Street, Paul Bird, and David H. DolphinCite this: J. Am. Chem. Soc. 1987, 109, 24, 7530–7531Publication Date (Print):November 1, 1987Publication History Published online1 May 2002Published inissue 1 November 1987https://pubs.acs.org/doi/10.1021/ja00258a047https://doi.org/10.1021/ja00258a047research-articleACS PublicationsRequest reuse...
Anti-cancer drug development involves enormous expenditure and risk. For rapid economical identification of novel, bioavailable anti-tumour chemicals, the use appropriate in vivo tumour models suitable for large-scale screening is key. Using a Drosophila Ras-driven model, we demonstrate that overgrowth can be curtailed by feeding larvae with chemicals have pharmacokinetics essential known efficacy against human cells. We then develop an 96-well plate chemical platform to carry out model. In...
Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei , causative agent of human African trypanosomiasis. Here we report discovery, synthesis, and development novel series TryR inhibitors based on 3,4-dihydroquinazoline scaffold. In addition, high resolution crystal structure TryR, alone complex with substrates from this series, presented. This represents first between noncovalent ligand enzyme. Structural studies revealed that upon binding...
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and currently clinical development melanoma, a tumor that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib demonstrate activity PRMT5, protein arginine methyltransferase indirect target CDK4, is essential for sensitivity. By indirectly suppressing PRMT5 activity, alters pre-mRNA splicing MDM4,...
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate H3K23 exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of to achieve therapeutic benefit has been a challenge. Here we describe identification highly potent, selective, orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from benzisoxazole series, which demonstrates anti-tumor...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInactivation of a .beta.-glucosidase through the accumulation stable 2-deoxy-2-fluoro-.alpha.-D-glucopyranosyl-enzyme intermediate: detailed investigationIan P. Street, Julie B. Kempton, and Stephen G. WithersCite this: Biochemistry 1992, 31, 41, 9970–9978Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIdentification of a covalent .alpha.-D-glucopyranosyl enzyme intermediate formed on .beta.-glucosidaseStephen G. Withers and Ian P. StreetCite this: J. Am. Chem. Soc. 1988, 110, 25, 8551–8553Publication Date (Print):December 1, 1988Publication History Published online1 May 2002Published inissue 1 December 1988https://pubs.acs.org/doi/10.1021/ja00233a045https://doi.org/10.1021/ja00233a045research-articleACS PublicationsRequest reuse...
Abstract Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase) is an enzyme in the isoprenoid biosynthetic pathway which catalyzes interconversion of primary five-carbon homoallylic and allylic building blocks. We report a substantially improved procedure for purification this from Saccharomyces cerevisiae. An amino-terminal sequence (35 amino acids) was obtained highly purified preparation IPP isomerase. Oligonucleotide probes based on protein were used to isolate...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNMR structural studies of the tight complex between a trifluoromethyl ketone inhibitor and 85-kDa human phospholipase A2Laird A. Trimble, Ian P. Street, Helene Perrier, Nathalie M. Tremblay, Philip K. Weech, Michael BernsteinCite this: Biochemistry 1993, 32, 47, 12560–12565Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November...
ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-xL Bcl-2. This class putative anticancer agents invariantly contains an acylsulfonamide core. We have designed synthesized a series novel quinazoline-based Bcl-2 that contain heterocyclic alternative to acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines presence 10% serum. comprises first successful demonstration quinazoline sulfonamide...
Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe hit-to-lead development selective Bcl-XL inhibitors originating from a high-throughput screening campaign. Small structural changes hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM). This molecular series exhibits drug-like characteristics, low weights (Mw 450), and unprecedented selectivity for...
The normal process of epithelial mesenchymal transition (EMT) is subverted by carcinoma cells to facilitate metastatic spread. Cancer rarely undergo a full conversion the phenotype, and instead adopt positions along epithelial-mesenchymal axis, propensity we refer as plasticity (EMP). EMP associated with increased risk metastasis in breast cancer consequent poor prognosis. Drivers towards state malignant include growth factor stimulation or exposure hypoxic conditions.We have examined two...
ADP-ribosylation is an important posttranslational protein modification that regulates diverse biological processes, controlled by dedicated transferases and hydrolases. Here, we show frequent deletions (∼30%) of the
This work describes the characterization of BNC210 (6-[(2,3-dihydro-1H-inden-2-yl)amino]-1-ethyl-3-(4-morpholinylcarbonyl)-1,8-naphthyridin-4(1H)-one), a selective, small molecule, negative allosteric modulator (NAM) α7 nicotinic acetylcholine receptors (α7 nAChR). With aim to discover non-sedating, anxiolytic compound, was identified during phenotypic screening focused medicinal chemistry library using mouse Light Dark (LD) box evaluate anxiolytic-like activity and Open Field (OF) (dark)...
Abstract Tumorigenic drivers of MYCN gene nonamplified neuroblastoma remain largely uncharacterized. Long noncoding RNAs (lncRNAs) regulate tumorigenesis, however, there is little literature on therapeutic targeting lncRNAs with small molecule compounds. Here PRKCQ‐AS1 identified as the lncRNA most overexpressed in nonamplified, compared ‐amplified, cell lines. expression controlled by super‐enhancers, and RNA bound to MSI2 protein. immunoprecipitation sequencing BMX mRNA transcript...