All Outputs (61)

Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer’s Disease Using OrbiSIMS and LC-MS/MS (2024)
Journal Article
Lu, L., Kotowska, A. M., Kern, S., Fang, M., Rudd, T. R., Alexander, M. R., Scurr, D. J., & Zhu, Z. (2024). Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer’s Disease Using OrbiSIMS and LC-MS/MS. Analytical Chemistry, https://doi.org/10.1021/acs.analchem.4c01201

Growing clinical evidence reveals that systematic molecular alterations in the brain occur 20 years before the onset of AD pathological features. Apolipoprotein E4 (ApoE4) is one of the most significant genetic risk factors for Alzheimer’s disease (A... Read More about Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer’s Disease Using OrbiSIMS and LC-MS/MS.

Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension (2024)
Journal Article
Wang, P., Zhu, H., Tian, J.-S., Zhu, W., Xu, S., Yao, H., Liu, J., Zhu, Z., Miao, C.-Y., & Xu, J. (2024). Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension. Journal of Medicinal Chemistry, 67(18), 16128-16144. https://doi.org/10.1021/acs.jmedchem.4c00626

Herein, a series of novel arylpiperazine (piperidine) derivatives were designed, synthesized, and evaluated for mechanisms of action through in vitro and in vivo studies. The most promising compound, II-13 (later named as MT-1207), is a potent α1 and... Read More about Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension.

Hit-to-Lead Optimization of the Natural Product Oridonin as Novel NLRP3 Inflammasome Inhibitors with Potent Anti-Inflammation Activity (2024)
Journal Article
He, C., Liu, J., Li, J., Wu, H., Jiao, C., Ze, X., Xu, S., Zhu, Z., Guo, W., Xu, J., & Yao, H. (2024). Hit-to-Lead Optimization of the Natural Product Oridonin as Novel NLRP3 Inflammasome Inhibitors with Potent Anti-Inflammation Activity. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.4c00504

Targeting NLRP3 inflammasome with inhibitors is a novel strategy for NLRP3-driven diseases. Herein, hit compound 5 possessing an attractive skeleton was identified from our in-house database of oridonin, and then a potential lead compound 32 was obta... Read More about Hit-to-Lead Optimization of the Natural Product Oridonin as Novel NLRP3 Inflammasome Inhibitors with Potent Anti-Inflammation Activity.

Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease (2024)
Journal Article
Wu, X., Ze, X., Qin, S., Zhang, B., Li, X., Gong, Q., …Xu, J. (2024). Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease. Molecules, 29(8), Article 1782. https://doi.org/10.3390/molecules29081782

Alzheimer’s disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoret... Read More about Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease.

Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease (2024)
Journal Article
Li, X., Sun, Y., Zhou, Z., Li, J., Liu, S., Chen, L., Shi, Y., Wang, M., Zhu, Z., Wang, G., & Lu, Q. (2024). Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease. Advanced Science, 11(18), Article 2308970. https://doi.org/10.1002/advs.202308970

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aβ, this study uses deep learning and a pharmacological approach to elucidate the potential of... Read More about Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Targeted intradermal delivery of alpha-arbutin-loaded dissolving polymeric microneedles visualized by three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) (2024)
Journal Article
Li, Z., Marlow, M., Scurr, D., & Zhu, Z. (2024). Targeted intradermal delivery of alpha-arbutin-loaded dissolving polymeric microneedles visualized by three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS). European Journal of Pharmaceutics and Biopharmaceutics, 196, Article 114181. https://doi.org/10.1016/j.ejpb.2024.114181

Hyperpigmentation, a prevalent dermatological condition characterized by melanin overproduction, poses treatment challenges due to the hydrophilicity of alpha-arbutin, a widely utilized tyrosinase inhibitor. This study investigates... Read More about Targeted intradermal delivery of alpha-arbutin-loaded dissolving polymeric microneedles visualized by three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS).

Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors (2023)
Journal Article
Hu, Z., Zhou, S., Li, J., Li, X., Zhou, Y., Zhu, Z., …Liu, J. (2023). Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors. Future Medicinal Chemistry, 15(20), 1823-1841. https://doi.org/10.4155/fmc-2023-0206

Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory acti... Read More about Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors.

Discovery of novel β-elemene hybrids with hydrogen sulfide-releasing moiety possessing cardiovascular protective activity for the treatment of atherosclerosis (2023)
Journal Article
Zhu, W., Wu, H., He, C., Zhu, H., Yao, H., Cao, Y., …Xu, J. (2023). Discovery of novel β-elemene hybrids with hydrogen sulfide-releasing moiety possessing cardiovascular protective activity for the treatment of atherosclerosis. RSC Medicinal Chemistry, https://doi.org/10.1039/d3md00447c

Herein, a series of novel β-elemene hybrids with different types of hydrogen sulfide (H2S) donors was designed and synthesized for the first time. In addition, all compounds were tested for H2S release in phosphate buffer solution assay, among which... Read More about Discovery of novel β-elemene hybrids with hydrogen sulfide-releasing moiety possessing cardiovascular protective activity for the treatment of atherosclerosis.

Hydrocortisone Mitigates Alzheimer’s-Related Cognitive Decline through Modulating Oxidative Stress and Neuroinflammation (2023)
Journal Article
Li, J., Chen, L., Liu, S., Sun, Y., Zhen, L., Zhu, Z., …Li, X. (2023). Hydrocortisone Mitigates Alzheimer’s-Related Cognitive Decline through Modulating Oxidative Stress and Neuroinflammation. Cells, 12(19), Article 2348. https://doi.org/10.3390/cells12192348

Alzheimer’s disease (AD), an age-related degenerative disorder, is characterized by β-amyloid deposition, abnormal phosphorylation of tau proteins, synaptic dysfunction, neuroinflammation, and oxidative stress. Despite extensive research, there are n... Read More about Hydrocortisone Mitigates Alzheimer’s-Related Cognitive Decline through Modulating Oxidative Stress and Neuroinflammation.

Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers (2023)
Journal Article
Vrettos, N., Wang, P., Wang, Y., Roberts, C. J., Xu, J., Yao, H., & Zhu, Z. (2023). Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers. Pharmaceutical Development and Technology, 28(8), 724-742. https://doi.org/10.1080/10837450.2023.2238822

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers... Read More about Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers.

Asiaticoside Mitigates Alzheimer’s Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function (2023)
Journal Article
Liu, S., Chen, L., Li, J., Sun, Y., Xu, Y., Li, Z., …Li, X. (2023). Asiaticoside Mitigates Alzheimer’s Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function. International Journal of Molecular Sciences, 24(15), Article 11976. https://doi.org/10.3390/ijms241511976

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, hallmarked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Due to the uncertainty of the pathogenesis of AD, strategies aimed at suppressing neuroinflammat... Read More about Asiaticoside Mitigates Alzheimer’s Disease Pathology by Attenuating Inflammation and Enhancing Synaptic Function.

Dual roles of demethylation in cancer treatment and cardio-function recovery (2023)
Journal Article
Li, X., Shen, D., Zhu, Z., Lyu, D., He, C., Sun, Y., …Wang, G. (2023). Dual roles of demethylation in cancer treatment and cardio-function recovery. Redox Biology, 64, Article 102785. https://doi.org/10.1016/j.redox.2023.102785

There are no effective therapeutic targets or strategies that simultaneously inhibit tumour growth and promote cardiac function recovery. Here, we analyzed targets for cancer treatments and cardiac repair, with demethylation emerging as a common fact... Read More about Dual roles of demethylation in cancer treatment and cardio-function recovery.

Synthesis and bioevaluation of novel stilbene-based derivatives as tubulin/HDAC dual-target inhibitors with potent antitumor activities in vitro and in vivo (2023)
Journal Article
Zhu, H., Zhu, W., Liu, Y., Gao, T., Zhu, J., Tan, Y., …Xu, S. (2023). Synthesis and bioevaluation of novel stilbene-based derivatives as tubulin/HDAC dual-target inhibitors with potent antitumor activities in vitro and in vivo. European Journal of Medicinal Chemistry, 257, Article 115529. https://doi.org/10.1016/j.ejmech.2023.115529

A series of novel stilbene-based derivatives were designed and synthesized as tubulin/HDAC dual-target inhibitors. Among forty-three target compounds, compound II-19k not only exhibited considerable antiproliferative activity in the hematological cel... Read More about Synthesis and bioevaluation of novel stilbene-based derivatives as tubulin/HDAC dual-target inhibitors with potent antitumor activities in vitro and in vivo.

Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer’s disease (2023)
Journal Article
Sun, Y., Li, J., A, N., Li, Z., Zhong, W., Chen, L., …Li, X. (2023). Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer’s disease. Frontiers in Immunology, 14, Article 1192940. https://doi.org/10.3389/fimmu.2023.1192940

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-β (Aβ), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the path... Read More about Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer’s disease.

Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation (2023)
Journal Article
Xue, S., Li, Z., Ze, X., Wu, X., He, C., Shuai, W., …Xu, S. (2023). Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation. Journal of Medicinal Chemistry, 66(7), 5099–5117. https://doi.org/10.1021/acs.jmedchem.3c00012

Excessive melanin deposition may lead to a series of skin disorders. The production of melanin is carried out by melanocytes, in which the enzyme tyrosinase performs a key role. In this work, we identified a series of novel tyrosinase inhibitor hybri... Read More about Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation.

Plant-Derived Products with Therapeutic Potential against Gastrointestinal Bacteria (2023)
Journal Article
Qassadi, F. I., Zhu, Z., & Monaghan, T. M. (2023). Plant-Derived Products with Therapeutic Potential against Gastrointestinal Bacteria. Pathogens, 12(2), Article 333. https://doi.org/10.3390/pathogens12020333

The rising burden of antimicrobial resistance and increasing infectious disease outbreaks, including the recent COVID-19 pandemic, has led to a growing demand for the development of natural products as a valuable source of leading medicinal compounds... Read More about Plant-Derived Products with Therapeutic Potential against Gastrointestinal Bacteria.

Discovery of Norbornene as a Novel Hydrophobic Tag Applied in Protein Degradation (2023)
Journal Article
Xie, S., Zhan, F., Zhu, J., Sun, Y., Zhu, H., Liu, J., …Xu, S. (2023). Discovery of Norbornene as a Novel Hydrophobic Tag Applied in Protein Degradation. Angewandte Chemie International Edition, 62(13), Article e202217246. https://doi.org/10.1002/anie.202217246

Hydrophobic tagging (HyT) is a potential therapeutic strategy for targeted protein degradation (TPD). Norbornene was discovered as an unprecedented hydrophobic tag in this study and was used to degrade the anaplastic lymphoma kinase (ALK) fusion prot... Read More about Discovery of Norbornene as a Novel Hydrophobic Tag Applied in Protein Degradation.

An update on the recent advances and discovery of novel tubulin colchicine binding inhibitors (2023)
Journal Article
Weng, H., Li, J., Zhu, H., Carver Wong, K. F., Zhu, Z., & Xu, J. (2023). An update on the recent advances and discovery of novel tubulin colchicine binding inhibitors. Future Medicinal Chemistry, 15(1), 73-95. https://doi.org/10.4155/fmc-2022-0212

Microtubules, formed by α- and β-tubulin heterodimer, are considered as a major target to prevent the proliferation of tumor cells. Microtubule-targeted agents have become increasingly effective anticancer drugs. However, due to the relatively sophis... Read More about An update on the recent advances and discovery of novel tubulin colchicine binding inhibitors.

Design, synthesis and biological evaluation of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine as anti-hepatocellular carcinoma agents (2023)
Journal Article
Chen, J., Duan, Y., Yang, K., Wang, J., Yan, J., Gu, C., …Xu, J. (2023). Design, synthesis and biological evaluation of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine as anti-hepatocellular carcinoma agents. Bioorganic and Medicinal Chemistry, 79, Article 117156. https://doi.org/10.1016/j.bmc.2023.117156

A series of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine were designed and synthesized with improved anti-hepatocellular carcinoma (HCC) activities. The optimal compound 4d showed strong activities against HepG2, Sk-Hep-1... Read More about Design, synthesis and biological evaluation of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine as anti-hepatocellular carcinoma agents.

Design, synthesis, and biological evaluation of novel protopanoxadiol derivatives based PROTACs technology for the treatment of lung cancer (2022)
Journal Article
Wang, P., Zhu, H., Liu, J., xie, S., Xu, S., Chen, Y., …Xu, J. (2023). Design, synthesis, and biological evaluation of novel protopanoxadiol derivatives based PROTACs technology for the treatment of lung cancer. Bioorganic Chemistry, 131, Article 106327. https://doi.org/10.1016/j.bioorg.2022.106327

Protopanoxadiol is a key active ingredient derived from Panax ginseng that is well-known to exhibit anti-tumor activity. Previous research focused on the natural protopanaxadiol derivative AD-1 has demonstrated that it possesses broad spectrum anti-t... Read More about Design, synthesis, and biological evaluation of novel protopanoxadiol derivatives based PROTACs technology for the treatment of lung cancer.