All Outputs (28)

Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor (2024)
Journal Article
Knight, R., Kilpatrick, L. E., Hill, S. J., & Stocks, M. J. (2024). Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor. ACS Medicinal Chemistry Letters, https://doi.org/10.1021/acsmedchemlett.4c00211

The P2Y2 receptor (P2Y2R) is a target for diseases including cancer, idiopathic pulmonary fibrosis, and atherosclerosis. However, there are insufficient P2Y2R antagonists available for validating P2Y2R function and future drug development. Evaluation... Read More about Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor.

Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein (2024)
Journal Article
Allison, M., Davie, R. L., Mogg, A. J., Hampton, S. L., Emsley, J., & Stocks, M. J. (2024). Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein. ACS Medicinal Chemistry Letters, 15(4), 501–509. https://doi.org/10.1021/acsmedchemlett.3c00572

Hereditary angioedema (HAE), a rare genetic disorder, is associated with uncontrolled plasma kallikrein (PKa) enzyme activity leading to the generation of bradykinin swelling in subcutaneous and submucosal membranes in various locations of the body.... Read More about Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein.

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.

Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport (2023)
Journal Article
Chu, Y., Wong, A., Chen, H., Ji, L., Qin, C., Feng, W., …Gershkovich, P. (2023). Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport. European Journal of Pharmaceutics and Biopharmaceutics, 191, 90-102. https://doi.org/10.1016/j.ejpb.2023.08.015

The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs) are one of the most important anatomical reservoirs of HIV. Suboptimal levels of an... Read More about Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport.

Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema (2022)
Journal Article
Davie, R. L., Edwards, H. J., Evans, D. M., Hodgson, S. T., Stocks, M. J., Smith, A. J., …Hampton, S. L. (2022). Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema. Journal of Medicinal Chemistry, 65(20), 13629-13644. https://doi.org/10.1021/acs.jmedchem.2c00921

Hereditary angioedema (HAE) is a rare genetic disorder in which patients experience sudden onset of swelling in various locations of the body. HAE is associated with uncontrolled plasma kallikrein (PKa) enzyme activity and generation of the potent in... Read More about Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema.

Is oral lipid-based delivery for drug targeting to the brain feasible? (2022)
Journal Article
Brookes, A., Ji, L., Bradshaw, T. D., Stocks, M., Gray, D., Butler, J., & Gershkovich, P. (2022). Is oral lipid-based delivery for drug targeting to the brain feasible?. European Journal of Pharmaceutics and Biopharmaceutics, 172, 112-122. https://doi.org/10.1016/j.ejpb.2022.02.004

This review outlines the feasibility of oral lipid-based targeted delivery of drugs to the brain, including permeation of the central nervous system's (CNS) protective blood–brain barrier (BBB). The structure of the BBB and disruption caused by varyi... Read More about Is oral lipid-based delivery for drug targeting to the brain feasible?.

Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients (2021)
Journal Article
Jewell, A., Williams, H., Hoad, C. L., Gellert, P. R., Ashford, M. B., Butler, J., …Gershkovich, P. (2021). Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients. Pharmaceutics, 13(9), Article 1343. https://doi.org/10.3390/pharmaceutics13091343

Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was... Read More about Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients.

Concurrent reactive oxygen species generation and aneuploidy induction contribute to thymoquinone anticancer activity (2021)
Journal Article
Al-Hayali, M., Garces, A., Stocks, M., Collins, H., & Bradshaw, T. D. (2021). Concurrent reactive oxygen species generation and aneuploidy induction contribute to thymoquinone anticancer activity. Molecules, 26(17), Article 5136. https://doi.org/10.3390/molecules26175136

Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa. Many studies have confirmed its anticancer actions. Herein, we investigated the different anticancer activities of, and considered resistance mechanisms to, TQ. MTT and... Read More about Concurrent reactive oxygen species generation and aneuploidy induction contribute to thymoquinone anticancer activity.

Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes (2021)
Journal Article
Sheriston, C., Medrano-Padial, C., Qin, C., Fischer, P. M., Feng, W., Chu, Y., …Ling, B. (2021). Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes. International Journal of Pharmaceutics, 602, Article 120621. https://doi.org/10.1016/j.ijpharm.2021.120621

The introduction of combination antiretroviral therapy (cART) led to substantial improvement in mortality and morbidity of HIV-1 infection. However, the poor penetration of antiretroviral agents to HIV-1 reservoirs limit the ability of the antiretrov... Read More about Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes.

Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol (2021)
Journal Article
Feng, W., Qin, C., Chu, Y. J., Berton, M., Lee, J. B., Zgair, A., …Gershkovich, P. (2021). Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol. European Journal of Pharmaceutics and Biopharmaceutics, 162, 43-49. https://doi.org/10.1016/j.ejpb.2021.02.013

© 2021 Elsevier B.V. Lipid-based formulations play a significant role in oral delivery of lipophilic drugs. Previous studies have shown that natural sesame oil promotes the intestinal lymphatic transport and oral bioavailability of the highly lipophi... Read More about Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol.

Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions (2020)
Journal Article
Sou, T., Soukarieh, F., Williams, P., Stocks, M. J., Cámara, M., & Bergström, C. A. S. (2020). Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions. ACS Omega, 5(40), 25733-25746. https://doi.org/10.1021/acsomega.0c03004

Copyright © 2020 American Chemical Society. For respiratory conditions, targeted drug delivery to the lungs could produce higher local concentrations with reduced risk of adverse events compared to systemic administration. Despite the increasing inte... Read More about Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions.

Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR (2020)
Journal Article
Grossman, S., Soukarieh, F., Richardson, W., Liu, R., Mashabi, A., Emsley, J., …Stocks, M. J. (2020). Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR. European Journal of Medicinal Chemistry, 208, Article 112778. https://doi.org/10.1016/j.ejmech.2020.112778

© 2020 The Authors Rising numbers of cases of multidrug- and extensively drug-resistant Pseudomonas aeruginosa over recent years have created an urgent need for novel therapeutic approaches to cure potentially fatal infections. One such approach is v... Read More about Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.

Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma (2020)
Journal Article
Qin, C., Feng, W., Chu, Y. J., Lee, J. B., Berton, M., Bettonte, S., …Gershkovich, P. (2020). Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma. Biomedical Chromatography, 34(11), Article e4934. https://doi.org/10.1002/bmc.4934

© 2020 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd A simple, sensitive and cost-effective HPLC-UV bioanalytical method for determination of lopinavir (LPV) in rat and human plasma was developed and validated. The plasm... Read More about Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma.

Modulators of CXCR4 and CXCR7/ACKR3 Function (2019)
Journal Article
Adlere, I., Caspar, B., Arimont, M., Dekkers, S., Visser, K., Stuijt, J., …Leurs, R. (2019). Modulators of CXCR4 and CXCR7/ACKR3 Function. Molecular Pharmacology, 96(6), 737-752. https://doi.org/10.1124/mol.119.117663

Copyright © 2019 by The Author(s). The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for hu... Read More about Modulators of CXCR4 and CXCR7/ACKR3 Function.

Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection (2018)
Journal Article
Sou, T., Kukavica-Ibrulj, I., Soukarieh, F., Halliday, N., Levesque, R. C., Williams, P., …Bergström, C. A. (2019). Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection. Journal of Pharmaceutical Sciences, 108(1), 630-640. https://doi.org/10.1016/j.xphs.2018.09.017

Antibiotic resistance is a major public health threat worldwide. In particular, about 80% of cystic fibrosis patients have chronic Pseudomonas aeruginosa (PA) lung infection resistant to many current antibiotics. We are therefore developing a novel c... Read More about Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives (2018)
Journal Article
Soukarieh, F., Williams, P., Stocks, M. J., & Camara, M. (in press). Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.8b00540

Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multi-drug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the sever... Read More about Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives.

Nucleoside based self-assembling drugs for localized drug delivery (2018)
Journal Article
Skilling, K. J., Stocks, M. J., Kellam, B., Ashford, M., Bradshaw, T., Burroughs, L., & Marlow, M. (in press). Nucleoside based self-assembling drugs for localized drug delivery. ChemMedChem, https://doi.org/10.1002/cmdc.201800063

We have synthesized a range of gelators based on nucleoside analogues gemcitabine and lamivudine, characterizing representative gels from the series using rheology and TEM. Growth inhibition studies of gemcitabine derivatives confirmed the feasibilit... Read More about Nucleoside based self-assembling drugs for localized drug delivery.

Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation (2018)
Journal Article
Citossi, F., Smith, T., Lee, J. B., Segal, J., Gershkovich, P., Stocks, M. J., …Marlow, M. (in press). Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation. Molecular Pharmaceutics, 15(4), https://doi.org/10.1021/acs.molpharmaceut.7b01106

Low molecular weight gelators (LMWGs) of chemotherapeutic drugs represent a valid alternative to the existing poly-mer-based formulations used for targeted delivery of anticancer drugs. Herein we report the design and development of novel self-assemb... Read More about Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation.

In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa (2018)
Journal Article
Soukarieh, F., Vico Oton, E., Dubern, J.-F., Gomes, J., Halliday, N., de Pilar Crespo, M., …Cámara, M. (2018). In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa. Molecules, 23(2), 1-15. https://doi.org/10.3390/molecules23020257

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sens... Read More about In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa.

From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor (2017)
Journal Article
Kindon, N., Davis, A., Dougall, I., Dixon, J., Johnson, T., Walters, I., …Stocks, M. (2017). From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor. Bioorganic and Medicinal Chemistry Letters, 27(21), 4849-4853. https://doi.org/10.1016/j.bmcl.2017.09.043

The G protein-coupled P2Y2 receptor, activated by ATP and UTP has been reported as a potential drug target for a wide range of important clinical conditions, such as tumor metastasis, kidney disorders, and in the treatment of inflammatory conditions.... Read More about From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor.