All Outputs (10)

Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation (2024)
Journal Article
Papadopoulou, D., Mavrikaki, V., Charalampous, F., Tzaferis, C., Samiotaki, M., Papavasileiou, K. D., Afantitis, A., Karagianni, N., Denis, M. C., Sanchez, J., Lane, R., Brotzakis, Z. F., Skretas, G., Georgiadis, D., Matralis, A. N., Kollias, G., Papavasileiou, K. D., Denis, M. C., & Matralis, A. N. (2024). Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation. Angewandte Chemie International Edition, 63(14), Article e202319157. https://doi.org/10.1002/anie.202319157

Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to... Read More about Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation.

Assessment of the potential of novel and classical opioids to induce respiratory depression in mice (2023)
Journal Article
Hill, R., Sanchez, J., Lemel, L., Antonijevic, M., Hosking, Y., Mistry, S. N., Kruegel, A. C., Javitch, J. A., Lane, J. R., & Canals, M. (2023). Assessment of the potential of novel and classical opioids to induce respiratory depression in mice. British Journal of Pharmacology, 180(24), 3160-3174. https://doi.org/10.1111/bph.16199

Background and Purpose
Opioid-induced respiratory depression limits the use of μ-opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respira... Read More about Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics (2023)
Journal Article
Bonifazi, A., Saab, E., Sanchez, J., Nazarova, A. L., Zaidi, S. A., Jahan, K., Katritch, V., Canals, M., Lane, J. R., & Newman, A. H. (2023). Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics. Journal of Medicinal Chemistry, 66(15), 10304–10341. https://doi.org/10.1021/acs.jmedchem.3c00417

A new generation of dual-target μ opioid receptor (MOR) agonist/dopamine D3 receptor (D3R) antagonist/partial agonists with optimized physicochemical properties was designed and synthesized. Combining in vitro cell-based on-target/off-target affinity... Read More about Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.

Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management (2021)
Journal Article
Bonifazi, A., Battiti, F. O., Sanchez, J., Zaidi, S. A., Bow, E., Makarova, M., Cao, J., Shaik, A. B., Sulima, A., Rice, K. C., Katritch, V., Canals, M., Lane, J. R., & Newman, A. H. (2021). Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management. Journal of Medicinal Chemistry, 64(11), 7778-7808. https://doi.org/10.1021/acs.jmedchem.1c00611

The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopami... Read More about Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14 (2021)
Journal Article
Wang, S., Foster, S. R., Sanchez, J., Corcilius, L., Larance, M., Canals, M., Stone, M. J., & Payne, R. J. (2021). Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14. ACS Chemical Biology, 16(6), 973-981. https://doi.org/10.1021/acschembio.1c00006

Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1–74), is a weak agonist for the chemokine receptor CCR1, but its act... Read More about Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14.

Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists (2020)
Journal Article
Gillis, A., Gondin, A. B., Kliewer, A., Sanchez, J., Lim, H. D., Alamein, C., Manandhar, P., Santiago, M., Fritzwanker, S., Schmidel, F., Katte, T. A., Reekie, T., Grimsey, N. L., Kassiou, M., Kellam, B., Krasel, C., Halls, M. L., Connor, M., Lane, J. R., Schulz, S., …Canals, M. (2020). Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists. Science Signaling, 13(625), Article eaaz3140. https://doi.org/10.1126/scisignal.aaz3140

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of... Read More about Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists.

Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism (2020)
Journal Article
Lane, J. R., Abramyan, A. M., Adhikari, P., Keen, A. C., Lee, K.-H., Sanchez, J., Verma, R. K., Lim, H. D., Yano, H., Javitch, J. A., & Shi, L. (2020). Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism. eLife, 9, Article e52189. https://doi.org/10.7554/elife.52189

By analyzing and simulating inactive conformations of the highly-homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/r... Read More about Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism.

Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1 (2019)
Journal Article
Sanchez, J., Lane, R., Canals, M., & Stone, M. J. (2019). Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1. International Journal of Molecular Sciences, 20(10), 1-15. https://doi.org/10.3390/ijms20102417

Leukocyte migration, a hallmark of the inflammatory response, is stimulated by the interactions between chemokines, which are expressed in injured or infected tissues, and chemokine receptors, which are G protein-coupled receptors (GPCRs) expressed i... Read More about Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1.

Ticks from diverse genera encode chemokine-inhibitory evasin proteins (2017)
Journal Article
Hayward, J., Sanchez, J., Perry, A., Huang, C., Rodriguez Valle, M., Canals, M., Payne, R. J., & Stone, M. J. (2017). Ticks from diverse genera encode chemokine-inhibitory evasin proteins. Journal of Biological Chemistry, 292(38), 15670-15680. https://doi.org/10.1074/jbc.M117.807255

To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules. In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named “evasins,” which bind to host c... Read More about Ticks from diverse genera encode chemokine-inhibitory evasin proteins.

Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2 (2017)
Journal Article
Huma, Z. E., Sanchez, J., Lim, H. D., Bridgford, J. L., Huang, C., Parker, B. J., Pazhamalil, J. G., Porebski, B. T., Pfleger, K. D. G., Lane, J. R., Canals, M., & Stone, M. J. (2017). Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2. Science Signaling, 10(480), Article eaai8529. https://doi.org/10.1126/scisignal.aai8529

Chemokines and their receptors collectively orchestrate the trafficking of leukocytes in normal immune function and inflammatory diseases. Different chemokines can induce distinct responses at the same receptor. In comparison to monocyte chemoattract... Read More about Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2.