Ximing Xu

• PhD
• Professor-level Senior Engineer at Marine Biomedical Research Institute of Qingdao

Redox‐based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs and probes of high specificity. In the context of anti‐ferroptosis research for neurological diseases, the inaccessibility of a blood–brain barrier (BBB) permeable small molecular ferroptosis inhibitor, and the lack of specific ferroptosis probe...

Redox‐based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs and probes of high specificity. In the context of anti‐ferroptosis research for neurological diseases, the inaccessibility of a blood‐brain barrier permeable (BBB) small molecular ferroptosis inhibitor, and the lack of specific ferroptosis probe...

Scoring functions (SFs) of molecular docking is a vital component of structure‐based virtual screening (SBVS). Traditional SFs yield their inherent shortage for idealized approximations and simplifications predicting the binding affinity. Complementarily, SFs based on deep learning (DL) have emerged as powerful tools for capturing intricate feature...

Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these reactions, NATs play a pivotal role in the detoxification...

Glutathione peroxidase 4 (GPX4) plays a crucial role in the ferroptosis pathway, emerging as a potential drug target in the treatment of refractory tumors. Unfortunately, the development of GPX4-targeted treatment has been very limited due to the poor selectivity and drug-like properties of current GPX4 inhibitors. Here, we report a proof-of-concep...

Asthma is a chronic airway inflammation that is considered a serious public health concern worldwide. Nobiletin (5,6,7,8,3′,4′-hexamethyl flavonoid), an important compound isolated from several traditional Chinese medicines, especially Citri Reticulatae Pericarpium, is widely used for a number of indications, including cancer, allergic diseases, an...

Background Ubiquitin-specific protease 7 (USP7) is one of the most widely studied deubiquitin enzymes (DUBs). The protein level of USP7 is highly expressed in a variety of malignant cancers, which suggests that it is a prognostic marker of cancers and a potential drug target for oncotherapy. Objective The aim of this study was to identify natural...

Personal protection from mosquito bites is essential for preventing mosquito‐borne diseases. Mosquito repellents are effective methods for preventing mosquito bites. Due to their ease of use and indirect skin contact, mosquito‐repellent stickers loaded with essential oils (EOs) have recently become favoured as novel spatial repellents. To discover...

Download page: https://github.com/biocheming/watvina

Screening of botanical spatial mosquito repellents from 64 essential oils and their interactions with odorant binding protein-3

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a “one stone kills two...

The molecular generation task stands as a pivotal step in the domains of computational chemistry and drug discovery, aiming to computationally generate molecular structures for specific properties. In contrast to previous models that focused primarily on SMILES strings or molecular graphs, our model placed a special emphasis on the substructure inf...

Insects rely on a family of seven-transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities such as sweet and bitter. Here we report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels, composed of one central pore d...

Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed. The SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) are vital proteins in viral replication and promising therapeutic targets. Additionally, PLpro also modulates ho...

Ginkgo biloba, as a medicinal plant in both traditional and western medicine, emerged as a potential therapeutic agent for the management of a variety of diseases, but ginkgo biflavones (bilobetin, isoginkgetin, and ginkgetin) application in cancer therapy and underlying mechanisms of action remained elusive. In the present study, we identified gin...

Hyperuricemia is a disease caused by disorder of purine metabolism, mainly due to insufficient renal excretion of uric acid. Urate transporter 1 (URAT1) is the most widely studied target of urate transporters, and used for uric acid (UA) reabsorption. This study used the AlphaFold2 algorithm to predict the structure of URAT1. Virtual screening and...

Leonurine (Leo) is a natural alkaloid extracted from Herba leonuri, which has many biological activities. However, whether leonurine has a protective effect on asthma remains unknown. The purpose of this study was to investigate the protective effect of leonurine on asthma. We evaluated its therapeutic effect and related signal transduction in LPS-...

Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spik...

Histone deacetylase 6 (HDAC6) is involved in multiple regulatory processes and emerges as a promising target for treating cancer and neurodegenerative diseases. Benefited from the unique sandwich conformation of ferrocene, a series of ferrocene-based hydroxamic acids have been developed as novel HDAC6 inhibitors in this paper, especially the two an...

Targeting sphingosine-1-phosphate receptor 2 (S1PR2) has been proved as a promising strategy to reverse 5-fluorouracil (5-FU) resistance. Here, we report the discovery of the novel JTE-013 derivative compound 37 h as a more effective S1PR2 antagonist to reverse 5-FU resistance in SW620/5-FU and HCT116DPD cells than JTE-013 and previously reported c...

A phthalimide probe (P1) possessing a hydroxylamine group on the benzene ring has been prepared for fluorescence sensing of copper ions. The detection is based on the reaction between hydroxylamine and copper ions, resulting in two fluorescent products through hydroxyl rearrangement and dehydroxylation reactions. P1 shows a specific and sensitive f...

Resistance to 5-FU reduces its clinical efficacy for the treatment of colorectal cancer. Sphingosine-1-phosphate receptor 2 (S1PR2) has emerged as a potential target to reverse 5-FU-resistance by inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). In this study, 38 novel S1PR2 antagonists based on aryl urea structure were designed a...

Analyzing the intrinsic dynamic characteristics of protein pockets is a key aspect to understanding the functional mechanism of proteins, which is conducive to the discovery and development of drugs. At present, the research on the dynamic characteristics of pockets mainly focuses on pocket stability, similarity, and physicochemical properties. How...

The New Delhi β-Lactamase 1 (NDM-1), one of the most prevalent types of metallo-β-lactamases, has attracted extensive attention since its discovery. Extensive efforts have been made to develop inhibitor of NDM-1, however, no inhibitor is available clinically so far. It is reported that Benzo[d][1], [2]selenazol-3(2H)-one derivatives as covalent NDM...

Molecular cavities play a critical role in our understanding of molecular phenomena. Recently, a number of works on the visual analysis of protein cavity dynamics have been developed to allow experts and users to interactively research dynamic cavity data. However, previous explorations are limited to studying cavity-lining amino acids and they lac...

Glutaminyl cyclases (QC) catalyze the cyclization of proteins and turn N-terminal glutamine or glutamic acid into N-terminal pyroglutamate, resulting in protection of proteins from aminopeptidases and an increase of their stabilities. The aberrant N-terminal pyroglutamate has been found in various diseases, including Alzheimer's disease (AD), Hunti...

The Papain‐Like proteases (PLpro) of SARS‐CoV‐2 plays a crucial role in viral replication and formation of non‐structural proteins. In order to find available inhibitors, the 3D structure of PLpro of SARS2 was obtained by homologous modeling, and we used this structure as a target to search inhibitors through molecular docking and MM/GBSA binding f...

Human protein tyrosine phosphatase 1B (PTP1B) is a ubiquitous non-receptor tyrosine phosphatase that serves as a major negative regulator of tyrosine phosphorylation cascades of metabolic and oncogenic importance such as the insulin, epidermal growth factor receptor (EGFR), and JAK/STAT pathways. Increasing evidence point to a key role of PTP1B-dep...

Transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable non-selective cation channel that acts as the primary cold sensor in humans. TRPM8 is also activated by ligands such as menthol, icilin, and phosphatidylinositol 4,5-bisphosphate (PIP2), and desensitized by Ca2+. Here we have determined electron cryo-microscopy structures...

Rheumatoid arthritis (RA) occurs in about 5 per 1,000 people and can lead to severe joint damage and disability. However, the knowledge of pathogenesis and treatment for RA remains limited. Here, we found that histone demethylase inhibitor GSK-J4 relieved collagen induced arthritis (CIA) symptom in experimental mice model, and the underlying mechan...

Naringenin, a citrus flavonoid that possessed various biological activities, had emerged as a potential therapeutic agent for the management of a variety of diseases, but naringenin derivatives’ application in cancer therapy and underlying mechanisms of action were not fully understood. Our recent work had shown that 4′,7-Di-O-methylnaringenin (DMN...

Ubiquitin-specific protease 7 (USP7) is one of the most extensively studied deubiquitinases. USP7 exhibits a high expression signature in various malignant tumors, suggesting that it is a marker of tumor prognosis and a potential drug target for anti-tumor therapy. In this study, virtual screening based on pharmacophore model and biological evaluat...

Hinokiflavone (HF), a natural biflavonoid that possesses various biological activities, has reported that HF could be a pre-mRNA splicing modulator, whereas its underlying mechanisms remain elusive. In the present study, we identified HF as a potential MDM2 inhibitor. What's more, we found that HF suppressed mdm2 mRNA synthesis at the transcription...

Myeloid differentiation factor 88 (MyD88) is a hub protein in the Toll-like receptor signaling pathway, which acts as a master switch for numerous inflammatory diseases, including acute lung injury (ALI). Although this protein is considered as a crucial therapeutic target, there are currently no clinically approved MyD88-targeting drugs. Based on p...

Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B inhibitor with an IC50 of 1.02 ± 0.17 μM. Cellular glucose consumption was sig...

The plant aluminum (Al)-activated malate transporter ALMT1 mediates the efflux of malate to chelate the Al in acidic soils and underlies the plant Al resistance. Here we present cryo-electron microscopy (cryo-EM) structures of Arabidopsis thaliana ALMT1 (AtALMT1) in the apo, malate-bound, and Al-bound states at neutral and/or acidic pH at up to 3.0...

Vibrio vulnificus is a zoonotic bacterium that is capable of causing highly lethal diseases in humans; this pathogen is responsible for 95% of all seafood-related deaths in the United States. Arylamine N-acetyltransferases (NAT, E.C. 2.3.1.5) is a major family of xenobiotic-metabolizing enzymes that can biotransform aromatic amine chemicals. In thi...

Significance Drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. It has been demonstrated that a new virtual screening approach with accelerated...

Polysaccharides have aroused considerable interest due to their diverse biological activities and low toxicity. In this study, we evaluated the effect of marine polysaccharide sulfated polymannuroguluronate (TGC161) on the leukopenia induced by chemotherapy. It is found that TGC161 ameliorates the leukopenia. Besides, TGC161 would promote CD4⁺ T ce...

Triple-negative breast cancer (TNBC) is a type of highly aggressive cancer that is hard to be cured by the commonly used chemotherapy, mainly due to the lack of effective tumor targeting ability of the current drugs and TNBC drug resistance. Therefore, development of novel strategies for precise and high-efficient therapy of TNBCs is urgently neede...

The analysis of molecular cavities, which are transport pathways in protein structures, is critical to the understanding of molecular phenomena. However, this work is challenging due to the high complexity and diversity of the macromolecular shapes in dynamic processes. In this paper, we propose a novel multiscale visualization method for visualizi...

The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays central roles in cancer cell growth and survival. Drug repurposing strategies have provided a valuable approach for developing antitumor drugs. Zelnorm (tegaserod maleate) was originally designed as an agonist of 5-hydroxytryptamine 4 receptor...

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and, thus, repurpos...

Integration of template‐based modeling, global sampling and precise scoring is crucial for the development of molecular docking programs with improved accuracy. We combined template‐based modeling and ab‐initio docking protocol as hybrid docking strategy called CoDock for the docking and scoring experiments of the seventh CAPRI edition. For CAPRI r...

Transglutaminases (TG) and arylamine N-acetyltransferases (NAT) are important family of enzymes. Although they catalyze different reactions and have distinct structures, these two families of enzymes share a spatially conserved catalytic triad (Cys, His, Asp residues). In active TGs, a conserved Trp residue located close to the triad cysteine is cr...

We present the results for CAPRI Round 46, the third joint CASP‐CAPRI protein assembly prediction challenge. The Round comprised a total of 20 targets including 14 homo‐oligomers and 6 heterocomplexes. Eight of the homo‐oligomer targets and one heterodimer comprised proteins that could be readily modeled using templates from the Protein Data Bank,...

We present the results for CAPRI Round 46, the 3rd joint CASP‐CAPRI protein assembly prediction challenge. The Round comprised a total of 20 targets including 14 homo‐oligomers and 6 hetero‐complexes. Eight of the homo‐oligomer targets and one hetero‐dimer comprised proteins that could be readily modeled using templates from the Protein Data Bank,...

Cover Picture. In this study, virtual screening is introduced to identify natural products targeting the wild‐type p53 Loop1/Sheet3 pocket. This pocket contains Cys124 site and is reported to be important to stabilize and reactive mutant p53. Considering of the high flexibility of Loop1, ensemble docking method is utilized to obtain druggable confo...

Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is mainly expressed in hematopoietic cells where it negatively regulates growth factor and cytokine signaling. PTPN2 is an important regulator of hematopoiesis and immune/inflammatory responses, as evidenced by loss of function mutations of PTPN2 in leukemia and lymphoma and knockout mice st...

Etoposide is a widely prescribed anticancer drug that is, however, associated with an increased risk of secondary leukemia. Although the molecular basis underlying the development of these leukemias remains poorly understood, increasing evidence implicates the interaction of etoposide metabolites [i.e., etoposide quinone (EQ)] with topoisomerase II...

The tumor‐suppressor function of p53 makes it an attractive drug target. Efforts were mostly put on stabilizing the functional p53 or reactivating the mutated p53. Previous studies show that small molecules targeting Loop1/Sheet3 (L1/S3) can reactivate the R175H‐p53 and stabilize p53 in vitro. Since L1/S3 pocket is shared by the mutate and the wild...

Melanoma is one of the most malignant and aggressive types of cancer worldwide. Fibroblast growth factor 2 (FGF2) is one of the critical regulators of melanoma angiogenesis and metastasis; thus, it might be an effective anti-cancer strategy to explore FGF2-targeting drug candidates from existing drugs. In this study, we evaluate the effect of the m...

Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effect...

β-Glucan has been reported to activate dendritic cells (DCs), and activated DCs, subsequently, promote Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. However, the mechanism that regulates the immune response of β-glucan-induced DCs has not been thoroughly elucidated to date. Recent studies have drawn attention to a strong rela...

In order to develop original water soluble antagonists of X‐linked inhibitor of apoptosis protein (XIAP), a novel bicyclic scaffold was designed based on 8,5‐fused bicyclic lactam. During its preparation, a spontaneous rearrangement from 8,5‐ to 7,5‐fused bicyclic lactam was observed and confirmed by MS and NMR analyses, in particular the HMBC spec...

Correction for ‘Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors’ by Zhaojun Sheng et al. , Med. Chem. Commun. , 2018, DOI: 10.1039/c8md00099a.

Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to modify natural product scaffolds. In this work, two s...

This is a commentary on the research article by Lu et al. recently published inBioscience ReportsThe GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N-acetyltransferase (GNAT) domain organization have been identified in actinobacteria by Lu et al. (2017). The ACT domain is fused to the GNAT domain, conferring amino acid-indu...

Glycemic control which can be efficaciously regulated by inhibiting α-glucosidase activity is an effective therapy for diabetes mellitus. This work is to investigate the kinetics and inhibition mechanism of oleanolic acid and ursolic acid on α-glucosidase. Oleanolic acid and ursolic acid exhibited potent inhibitory activities with IC50 values of (6...

A large number of structures of anti-cancer drug targets have been solved and deposited to the protein data bank already. Identification of the targets for marine compounds with anti-tumor activity presents a challenge for marine natural products scientists. In this study, fast and efficient computational reverse docking was applied to predict the...

The antimicrobial mechanism of naringenin, one of the citrus antibacterial flavonoids against foodborne Staphylococcus aureus ATCC 6538 was investigated in this work. Analysis of gas chromatography−mass spectrometry (GC−MS) and fluorescence showed that the relative low concentrations of naringenin caused perturbations in membrane fatty acid composi...

Thiram (tetramethylthiuram disulfide) is a representative dithiocarbamate (DTC) pesticide used in both the field and as a seed protectant. The widespread use of Thiram and other DTC pesticides has raised concerns for health as these compounds can exert neuropathic, endocrine disruptive and carcinogenic effects. These toxic effects are thought to re...

Quercetin, a flavonoid compound, was found to inhibit both monophenolase and diphenolase activities of tyrosinase, and its inhibition against diphenolase activity was in a reversible and competitive manner with an IC50 value of (3.08 ± 0.74) × 10− 5 mol L− 1. Quercetin bound to tyrosinase driven by hydrophobic interaction, thereby resulted in a con...

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the effic...

The alarming growth of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) has become a major global health hazard. Therefore, urgent demand for new antibiotics with a unique mechanism of action is very necessary. The present study reports the design, synthesis, and anti...

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limi...

Aromatic amines (AAs) are chemicals of industrial, pharmacological and environmental relevance. Certain AAs, such as 4-aminobiphenyl (4-ABP), are human carcinogens that require enzymatic metabolic activation to reactive chemicals to form genotoxic DNA adducts. Arylamine N-acetyltransferases (NAT) are xenobiotic metabolizing enzymes (XME) that play...

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined in complex with CoA. The F42W mutant of (RHILO)NAT1 was...

Introduction: Thiocarbamates are chemicals widely used as pesticides. Occupational exposure is associated with acute intoxication. Populations can be exposed through food and water. Moreover, certain thiocarbamates are used clinically. The widespread use of thiocarbamates raises many issues regarding their toxicological and pharmacological impact....

Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution m...

Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural and functional characterization of an arylamine N-acet...

The JAK2/STAT3 signaling pathway plays a critical role in oncogenesis and malignancy, which makes it a promising anticancer target. We report four N(6)-substituted adenosine analogues (AAs) as potential JAK2/STAT3 inhibitors identified through a STAT3-based high-throughput drug screening system. These AAs exhibited selective anti-cancer activity on...

A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae wer...

This letter is a comment on Zhou et al. (2013). Arylamine N-acetyltransferases: a structural perspective. Br J Pharmacol 169: 748-760. To view this article visit http://dx.doi.org/10.1111/bph.12182.

Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis,...

Muscle glycogen phosphorylase (GP) plays an important role in muscle functions. Mercury has toxic effects in skeletal muscle leading to muscle weakness or cramps. However, the mechanisms underlying these toxic effects are poorly understood. We report that GP is irreversibly inhibited by inorganic (Hg(2+)) and organic (CH3Hg(+)) mercury (IC50=380 nM...

Acrolein is an electrophilic α, β-unsaturated aldehyde of industrial, pharmaceutical and toxicological importance to which we are exposed in environmental, occupational and therapeutic situations. Acrolein is known to exert different biological effects through reactions with cellular macromolecules such as DNA, certain proteins or glutathione. In m...

Our previous studies have demonstrated that PMS1077, a platelet-activating factor (PAF) antagonist, could induce apoptosis of Raji cells. However, the mechanism of action has not yet been determined. The nuclear transcription factor-kappa B (NF-κB) signaling pathway plays a critical role in tumor cell survival, proliferation, invasion, metastasis,...

PMS1077 rather than PMS601 inhibited TNF-α-induced NF-κB/P65 nuclear translocation. DU145 cells were pretreated with PMS1077 (50 µM) or PMS601 (50 µM) for 6 h and followed by TNF-α (20 ng/ml) stimulation for 0.5 h. TPCA-1 (2 µM) and DMSO were used as positive NF-κB inhibitor and negative control, respectively. After treatment, cells were stained wi...

PMS1077 inhibited PMA induced expression of NF-κB regulated reporter gene. PC3-NF-κB-Luciferase cells were treated with PMS1077 or PMS601 at final concentration as indicated. TPCA-1 (2 µM) is a specific inhibitor of NF-κB for positive control and DMSO as vehicle. Then cells were left untreated or exposed to PMA (20 ng/ml) for 12 h. Luciferase activ...