Outputs (59)

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists (2024)
Journal Article
Cullum, S. A., Platt, S., Dale, N., Isaac, O. C., Wragg, E. S., Soave, M., …Hill, S. J. (2024). Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists. Communications Biology, 7(1), Article 417. https://doi.org/10.1038/s42003-024-06128-2

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conform... Read More about Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists.

CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans (2024)
Journal Article
White, C. W., Platt, S., Kilpatrick, L. E., Dale, N., Abhayawardana, R. S., Dekkers, S., …Hill, S. J. (2024). CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans. Science Signaling, 17(828), Article abl3758. https://doi.org/10.1126/scisignal.abl3758

CXCL17 is a chemokine principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and... Read More about CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans.

Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats (2023)
Journal Article
Pannucci, P., Van Daele, M., Cooper, S. L., Wragg, E. S., March, J., Groenen, M., …Woolard, J. (2023). Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats. Biochemical Pharmacology, Article 116007. https://doi.org/10.1016/j.bcp.2023.116007

Receptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatini... Read More about Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats.

Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3) (2023)
Journal Article
Dekkers, S., Comez, D., Karsai, N., Arimont-Segura, M., Canals, M., Caspar, B., …Stocks, M. J. (2023). Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3). ACS Medicinal Chemistry Letters, 15(1), 143–148. https://doi.org/10.1021/acsmedchemlett.3c00469

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluoresc... Read More about Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3).

Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells (2023)
Journal Article
Hill, S. J., & Kilpatrick, L. E. (2023). Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells. British Journal of Pharmacology, https://doi.org/10.1111/bph.16185

Equilibrium binding assays are one of the mainstays of current drug discovery efforts to evaluate the interaction of drugs with receptors in membranes and intact cells. However, in recent years, there has been increased focus on the kinetics of the d... Read More about Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells.

Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET (2023)
Journal Article
Van Daele, M., Kilpatrick, L. E., Woolard, J., & Hill, S. J. (2023). Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET. Biochemical Pharmacology, 214, Article 115672. https://doi.org/10.1016/j.bcp.2023.115672

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, proliferation and migration of vascular endothelial cells. It is well known that cardiovascular safety liability for a wide range of small molecule tyrosine kinase in... Read More about Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET.

Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells (2023)
Journal Article
Ogrodzinski, L., Platt, S., Goulding, J., Alexander, C., Farr, T. D., Woolard, J., …Kilpatrick, L. E. (2023). Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells. iScience, 26(7), Article 107232. https://doi.org/10.1016/j.isci.2023.107232

E-selectin is expressed on endothelial cells in response to inflammatory cytokines and mediates leukocyte rolling and extravasation. However, studies have been hampered by lack of experimental approaches to monitor expression in real time in living c... Read More about Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells.

Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes (2023)
Journal Article
Lay, C. S., Isidro-Llobet, A., Kilpatrick, L. E., Craggs, P. D., & Hill, S. J. (2023). Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes. Nature Communications, 14, Article 2882. https://doi.org/10.1038/s41467-023-38541-2

Association of single nucleotide polymorphisms in the IL-23 receptor with several auto-inflammatory diseases, led to the heterodimeric receptor and its cytokine-ligand IL-23, becoming important drug targets. Successful antibody-based therapies direct... Read More about Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes.

Plasma membrane preassociation drives β-arrestin coupling to receptors and activation (2023)
Journal Article
Grimes, J., Koszegi, Z., Lanoiselée, Y., Miljus, T., O’Brien, S. L., Stepniewski, T. M., …Calebiro, D. (2023). Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell, 186(10), 2238-2255. https://doi.org/10.1016/j.cell.2023.04.018

β-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-β-arrestin interactions at the plasma membrane of living cells remain elusive. Her... Read More about Plasma membrane preassociation drives β-arrestin coupling to receptors and activation.

Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor (2023)
Journal Article
Dekkers, S., Caspar, B., Goulding, J., Kindon, N. D., Kilpatrick, L. E., Stoddart, L. A., …Stocks, M. J. (2023). Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor. Journal of Medicinal Chemistry, 66(7), 5208-5222. https://doi.org/10.1021/acs.jmedchem.3c00151

The C-X-C chemokine receptor type 4, or CXCR4, is a chemokine receptor found to promote cancer progression and metastasis of various cancer cell types. To investigate the pharmacology of this receptor, and to further elucidate its role in cancer, nov... Read More about Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor.