Search

Your search keyword '"Spring, David R."' showing total 108 results
Start Over Author "Spring, David R." Publisher wiley
108 results on '"Spring, David R."'

4. Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI‐001 in in vitro Models of Prostate Cancer Drug Resistance

Author

Nicolescu, Radu Costin Bizga, Maylin, Zoe R, Pérez-Areales, Francisco Javier, Iegre, Jessica, Pandha, Hardev S, Asim, Mohammad, Spring, David R, Nicolescu, Radu Costin Bizga [0000-0003-2038-0672], Maylin, Zoe R [0000-0001-6647-213X], Pérez-Areales, Francisco Javier [0000-0001-9525-9346], Iegre, Jessica [0000-0002-9074-653X], Asim, Mohammad [0000-0002-2074-5929], Spring, David R [0000-0001-7355-2824], and Apollo - University of Cambridge Repository

Subjects
Male, Pharmacology, enzalutamide, EPI-001, Organic Chemistry, prostate cancer, Biochemistry, Prostatic Neoplasms, Castration-Resistant, Receptors, Androgen, Drug Resistance, Neoplasm, androgen receptor, Cell Line, Tumor, Nitriles, Drug Discovery, Androgen Receptor Antagonists, Humans, Molecular Medicine, General Pharmacology, Toxicology and Pharmaceutics, dual inhibitors
Abstract

Funder: Prostate Cancer Foundation; Id: http://dx.doi.org/10.13039/100000892, Funder: UKRI; Id: http://dx.doi.org/10.13039/100014013, Funder: Trinity College Cambridge, Funder: University of Surrey PhD studentship award, Androgen receptor targeted therapies for prostate cancer have serious limitations in advanced stages of the disease. While resistance to the FDA-approved enzalutamide is extensively documented, novel therapies based on epichlorohydrin scaffolds (EPI) are currently in clinical trials, but display suboptimal pharmacokinetics. Herein, we report the synthesis and biological characterisation of a novel class of compounds designed through covalently linking enzalutamide and EPI-001 through various triazole based linkers. The compounds display an 18 to 53 fold improvement in the cell killing potency towards C4-2b prostate cancer (PCa) cells compared to the gold standards of therapy, enzalutamide and EPI-001. The most promising compounds were proven to exhibit their toxicity exclusively through androgen receptor (AR) mediated pathways. This work sets the basis for the first class of hybrid AR inhibitors which successfully combine two drug moieties - EPI-001 and enzalutamide - into the same molecule.

Published
2022

8. Synthesis of Structurally Diverse N-Substituted Quaternary-Carbon-Containing Small Molecules from α,α-Disubstituted Propargyl Amino Esters

Author

Mateu, Natalia, Kidd, Sarah L, Kalash, Leen, Sore, Hannah F, Madin, Andrew, Bender, Andreas, Spring, David R, Mateu, Natalia [0000-0001-9451-0666], Spring, David R [0000-0001-7355-2824], and Apollo - University of Cambridge Repository

Subjects
molecular diversity, medicinal chemistry, quaternary stereocenters, diversity-oriented synthesis, human activities, drug discovery
Abstract

N-containing quaternary stereocenters represent important motifs in medicinal chemistry. However, due to their inherently sterically hindered nature, they remain underrepresented in small molecule screening collections. As such, the development of synthetic routes to generate small molecules that incorporate this particular feature are highly desirable. Herein, we describe the diversity-oriented synthesis (DOS) of a diverse collection of structurally distinct small molecules featuring this three-dimensional (3D) motif. The subsequent derivatisation and the stereoselective synthesis exemplified the versatility of this strategy for drug discovery and library enrichment. Chemoinformatic analysis revealed the enhanced sp3 character of the target library and demonstrated that it represents an attractive collection of biologically diverse small molecules with high scaffold diversity.

Published
2018
Full Text
View/download PDF

12. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

Author

Wu, Yuteng, Olsen, Lasse B., Lau, Yu Heng, Jensen, Claus Hatt, Rossmann, Maxim, Baker, Ysobel R., Sore, Hannah F., Collins, Súil, Spring, David R., Rossmann, Maxim [0000-0001-8811-3277], Sore, Hannah [0000-0002-6542-0394], Spring, David [0000-0001-7355-2824], and Apollo - University of Cambridge Repository

Subjects
Molecular Structure, Communication, Proto-Oncogene Proteins c-mdm2, Photoaffinity Labels, stapled peptide, Ligands, linker, Communications, Benzophenones, Cross-Linking Reagents, MDM2, click chemistry, Peptides, photoaffinity labeling
Abstract

Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo‐crosslinking motif and a peptide stapling reagent. Using double‐click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo‐crosslinking amino acid. When applied to a p53‐derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull‐down assays, and can be used to investigate the target selectivity of stapled peptides.

Published
2016

49. Aryl-Aryl Bond Formation by the Fluoride-Free Cross-Coupling of Aryldisiloxanes with Aryl Bromides

Author

Boehner, Christine M., primary, Frye, Elizabeth C., additional, O'Connell, Kieron M. G., additional, Galloway, Warren R. J. D., additional, Sore, Hannah F., additional, Dominguez, Patricia Garcia, additional, Norton, David, additional, Hulcoop, David G., additional, Owen, Martin, additional, Turner, Gillian, additional, Crawford, Claire, additional, Horsley, Helen, additional, and Spring, David R., additional

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results