All Outputs (46)

Delivery of imiquimod to intestinal lymph nodes following oral administration (2024)
Journal Article
Chen, H., Ji, L., Wong, A., Chu, Y., Feng, W., Zhu, Y., Wang, J., Comeo, E., Kim, D.-H., Stocks, M. J., & Gershkovich, P. (in press). Delivery of imiquimod to intestinal lymph nodes following oral administration. International Journal of Pharmaceutics,

Intestinal lymph nodes are involved in the progression of colorectal cancer (CRC). Tumours suppress the activation of dendritic cells (DCs) in draining lymph nodes, diminishing anti-cancer immune response. Imiquimod (IMQ) facilitates DCs activation v... Read More about Delivery of imiquimod to intestinal lymph nodes following oral administration.

Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory (2024)
Journal Article
Wang, D., Pattenden, G., Fow, K. L., Stocks, M. J., Hirst, J. D., & Tang, B. (2024). Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory. Journal of Organic Chemistry, 89(18), 12946-12956. https://doi.org/10.1021/acs.joc.4c00859

Density functional theory (B3LYP-D3(BJ) and ωB97XD) calculations have been used to assess the stereochemical outcomes of the proposed transannular [4 + 2] cycloaddition pathway for the biosynthesis of mandapamate and isomandapamate from macrocyclic i... Read More about Theoretical Study on the Biosynthesis of the Mandapamates: Mechanistic Insights Using Density Functional Theory.

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, 15(7), 1127-1135. 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.

Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections (2024)
Journal Article
Soukarieh, F., Mashabi, A., Richardson, W., Oton, E. V., Romero, M., Dubern, J., …Cámara, M. (2024). Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections. Journal of Medicinal Chemistry, 67(2), 1008-1023. https://doi.org/10.1021/acs.jmedchem.3c00973

Pseudomonas aeruginosa is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to c... Read More about Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections.

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).

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.

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.

Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms (2023)
Journal Article
Soukarieh, F., Gurnani, P., Romero, M., Halliday, N., Stocks, M., Alexander, C., & Cámara, M. (2023). Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms. ACS Macro Letters, 12(3), 314-319. https://doi.org/10.1021/acsmacrolett.2c00699

Antimicrobial resistance (AMR) is a global threat to public health with a forecast of a negative financial impact of one trillion dollars per annum, hence novel therapeutics are urgently needed. The resistance of many bacteria against current drugs i... Read More about Design of Quorum Sensing Inhibitor–Polymer Conjugates to Penetrate Pseudomonas aeruginosa Biofilms.

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.

Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs (2022)
Journal Article
Ayre, J., Redmond, J. M., Vitulli, G., Tomlinson, L., Weaver, R., Comeo, E., …Stocks, M. J. (2022). Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs. Journal of Medicinal Chemistry, 65(14), 9802-9818. https://doi.org/10.1021/acs.jmedchem.2c00416

A major limitation of pulmonary delivery is that drugs can exhibit suboptimal pharmacokinetic profiles resulting from rapid elimination from the pulmonary tissue. This can lead to systemic side effects and a short duration of action. A series of diba... Read More about Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs.

Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol (2022)
Journal Article
Feng, W., Qin, C., Abdelrazig, S., Bai, Z., Raji, M., Darwish, R., …Gershkovich, P. (2022). Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol. International Journal of Pharmaceutics, 624, Article 121947. https://doi.org/10.1016/j.ijpharm.2022.121947

Although natural sesame oil has been shown to facilitate the lymphatic delivery and oral bioavailability of the highly lipophilic drug cannabidiol (CBD), considerable variability remains an unresolved challenge. Vegetable oils differ substantially in... Read More about Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol.

Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle (2022)
Journal Article
Jewell, A., Brookes, A., Feng, W., Ashford, M., Gellert, P., Butler, J., …Gershkovich, P. (2022). Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle. European Journal of Pharmaceutics and Biopharmaceutics, 174, 29-34. https://doi.org/10.1016/j.ejpb.2022.03.014

Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the... Read More about Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle.

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.

Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa (2021)
Journal Article
Soukarieh, F., Mashabi, A., Richardson, W., Oton, E. V., Romero, M., Roberston, S. N., …Cámara, M. (2021). Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa. ACS Infectious Diseases, 7(9), 2666-2685. https://doi.org/10.1021/acsinfecdis.1c00175

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is... Read More about Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa.

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.