LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Discovery of PLD4 modulators by high-throughput screening and kinetic analysis.

    Lee, Jinny Claire / Shirey, Ryan J / Turner, Lewis D / Park, Hyeri / Lairson, Luke L / Janda, Kim D

    Results in chemistry

    2024  Volume 7

    Abstract: Phospholipase D3 (PLD3) and D4 (PLD4) are endolysosomal exonucleases of ssDNA and ssRNA that regulate innate immunity. Polymorphisms of these enzymes are correlated with numerous human diseases, including Alzheimer's, rheumatoid arthritis, and systemic ... ...

    Abstract Phospholipase D3 (PLD3) and D4 (PLD4) are endolysosomal exonucleases of ssDNA and ssRNA that regulate innate immunity. Polymorphisms of these enzymes are correlated with numerous human diseases, including Alzheimer's, rheumatoid arthritis, and systemic sclerosis. Pharmacological modulation of these immunoregulatory proteins may yield novel immunotherapies and adjuvants. A previous study reported a high-throughput screen (
    Language English
    Publishing date 2024-02-08
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2211-7156
    ISSN (online) 2211-7156
    DOI 10.1016/j.rechem.2024.101349
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Modulators of immunoregulatory exonucleases PLD3 and PLD4 identified by high-throughput screen.

    Shirey, Ryan J / Turner, Lewis D / Lairson, Luke L / Janda, Kim D

    Bioorganic & medicinal chemistry letters

    2021  Volume 49, Page(s) 128293

    Abstract: PLD3 and PLD4 have recently been revealed to be endosomal exonucleases that regulate the innate immune response by digesting the ligands of nucleic acid sensors. These enzymes can suppress RNA and DNA innate immune sensors like toll-like receptor 9, and ... ...

    Abstract PLD3 and PLD4 have recently been revealed to be endosomal exonucleases that regulate the innate immune response by digesting the ligands of nucleic acid sensors. These enzymes can suppress RNA and DNA innate immune sensors like toll-like receptor 9, and PLD4-deficent mice exhibit inflammatory disease. Targeting these immunoregulatory enzymes presents an opportunity to indirectly regulate innate immune nucleic acid sensors that could yield immunotherapies, adjuvants, and nucleic acid drug stabilizers. To aid in delineating the therapeutic potential of these targets, we have developed a high-throughput fluorescence enzymatic assay to identify modulators of PLD3 and PLD4. Screening of a diversity library (N = 17952) yielded preferential inhibitors of PLD3 and PLD4 in addition to a PLD3 selective activator. The modulation models of these compounds were delineated by kinetic analysis. This work presents an inexpensive and simple method to identify modulators of these immunoregulatory exonucleases.
    MeSH term(s) Enzyme Activators/chemistry ; Enzyme Assays ; Enzyme Inhibitors/chemistry ; Exodeoxyribonucleases/antagonists & inhibitors ; Fluorescent Dyes/chemistry ; High-Throughput Screening Assays ; Humans ; Nitrophenols/chemistry ; Phospholipase D/antagonists & inhibitors ; Thymine Nucleotides/chemistry ; Umbelliferones/chemistry
    Chemical Substances Enzyme Activators ; Enzyme Inhibitors ; Fluorescent Dyes ; Nitrophenols ; Thymine Nucleotides ; Umbelliferones ; Exodeoxyribonucleases (EC 3.1.-) ; PLD4 protein, human (EC 3.1.-) ; PLD3 protein, human (EC 3.1.4.4) ; Phospholipase D (EC 3.1.4.4)
    Language English
    Publishing date 2021-07-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2021.128293
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3203: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Noninvasive Urine Biomarker Lateral Flow Immunoassay for Monitoring Active Onchocerciasis.

    Shirey, Ryan J / Globisch, Daniel / Eubanks, Lisa M / Hixon, Mark S / Janda, Kim D

    ACS infectious diseases

    2018  Volume 4, Issue 10, Page(s) 1423–1431

    Abstract: The parasitic disease onchocerciasis is the second leading cause of preventable blindness, afflicting more than 18 million people worldwide. Despite an available treatment, ivermectin, and control efforts by the World Health Organization, onchocerciasis ... ...

    Abstract The parasitic disease onchocerciasis is the second leading cause of preventable blindness, afflicting more than 18 million people worldwide. Despite an available treatment, ivermectin, and control efforts by the World Health Organization, onchocerciasis remains a burden in many regions. With an estimated 120 million people living in areas at risk of infection, efforts are now shifting from prevention to surveillance and elimination. The lack of a robust, point-of-care diagnostic for an active Onchocerca infection has been a limiting factor in these efforts. Previously, we reported the discovery of the biomarker N-acetyl-tyramine- O-glucuronide (NATOG) in human urine samples and its ability to track treatment progression between medicated patients relative to placebo; we also established its capability to monitor disease burden in a jird model. NATOG is a human-produced metabolite of tyramine, which itself is produced as a nematode neurotransmitter. The ability of NATOG to distinguish between active and past infection overcomes the limitations of antibody biomarkers and PCR methodologies. Lateral flow immunoassay (LFIA) diagnostics offer the versatility and simplicity to be employed in the field and are inexpensive enough to be utilized in large-scale screening efforts. Herein, we report the development and assessment of a NATOG-based urine LFIA for onchocerciasis, which accurately identified 85% of analyzed patient samples ( N = 27).
    MeSH term(s) Animals ; Antibodies, Monoclonal, Murine-Derived/immunology ; Biomarkers/urine ; Data Accuracy ; Gold/chemistry ; Humans ; Immunoassay/methods ; Mass Spectrometry ; Metal Nanoparticles/chemistry ; Neglected Diseases/diagnosis ; Neglected Diseases/prevention & control ; Neglected Diseases/urine ; Onchocerca volvulus ; Onchocerciasis/diagnosis ; Onchocerciasis/prevention & control ; Onchocerciasis/urine ; Point-of-Care Testing ; Surface Plasmon Resonance ; Tyramine/analogs & derivatives ; Tyramine/immunology ; Tyramine/urine
    Chemical Substances Antibodies, Monoclonal, Murine-Derived ; Biomarkers ; tyramine glucuronide (27972-85-6) ; Gold (7440-57-5) ; Tyramine (X8ZC7V0OX3)
    Language English
    Publishing date 2018-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.8b00163
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Synthetic fluorescent MYC probe: Inhibitor binding site elucidation and development of a high-throughput screening assay.

    Shirey, Ryan J / Hart, Jonathan R / Sridharan, BanuPriya / Novick, Scott J / Turner, Lewis D / Zhou, Bin / Nielsen, Alexander L / Eubanks, Lisa M / Ueno, Lynn / Hixon, Mark S / Lairson, Luke L / Spicer, Timothy P / Scampavia, Louis D / Griffin, Patrick R / Vogt, Peter K / Janda, Kim D

    Bioorganic & medicinal chemistry

    2021  Volume 42, Page(s) 116246

    Abstract: We report the discovery of a fluorescent small molecule probe. This probe exhibits an emission increase in the presence of the oncoprotein MYC that can be attenuated by a competing inhibitor. Hydrogen-deuterium exchange mass spectrometry analysis, ... ...

    Abstract We report the discovery of a fluorescent small molecule probe. This probe exhibits an emission increase in the presence of the oncoprotein MYC that can be attenuated by a competing inhibitor. Hydrogen-deuterium exchange mass spectrometry analysis, rationalized by induced-fit docking, suggests it binds to the "coiled-coil" region of the leucine zipper domain. Point mutations of this site produced functional MYC constructs resistant to inhibition in an oncogenic transformation assay by compounds that displace the probe. Utilizing this probe, we have developed a high-throughput assay to identify MYC inhibitor scaffolds. Screening of a diversity library (N = 1408, 384-well) and a library of pharmacologically active compounds (N = 1280, 1536-well) yielded molecules with greater drug-like properties than the probe. One lead is a potent inhibitor of oncogenic transformation and is specific for MYC relative to resistant mutants and transformation-inducing oncogenes. This method is simple, inexpensive, and does not require protein modification, DNA binding, or the dimer partner MAX. This assay presents an opportunity for MYC inhibition researchers to discover unique scaffolds.
    MeSH term(s) Binding Sites/drug effects ; Dose-Response Relationship, Drug ; Drug Development ; Fluorescent Dyes/chemical synthesis ; Fluorescent Dyes/chemistry ; Fluorescent Dyes/pharmacology ; High-Throughput Screening Assays ; Humans ; Molecular Structure ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/metabolism ; Structure-Activity Relationship
    Chemical Substances Fluorescent Dyes ; Proto-Oncogene Proteins c-myc
    Language English
    Publishing date 2021-06-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2021.116246
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3815: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG).

    Globisch, Daniel / Eubanks, Lisa M / Shirey, Ryan J / Pfarr, Kenneth M / Wanji, Samuel / Debrah, Alexander Y / Hoerauf, Achim / Janda, Kim D

    Bioorganic & medicinal chemistry letters

    2017  Volume 27, Issue 15, Page(s) 3436–3440

    Abstract: The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual ... ...

    Abstract The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.
    MeSH term(s) Animals ; Biomarkers/urine ; Chromatography, Liquid/methods ; Glucuronides/metabolism ; Glucuronides/urine ; Humans ; Limit of Detection ; Mass Spectrometry/methods ; Metabolomics/methods ; Neglected Diseases/metabolism ; Neglected Diseases/urine ; Onchocerca volvulus/isolation & purification ; Onchocerca volvulus/metabolism ; Onchocerciasis/metabolism ; Onchocerciasis/urine ; Tyramine/analogs & derivatives ; Tyramine/metabolism ; Tyramine/urine
    Chemical Substances Biomarkers ; Glucuronides ; N-acetyltyramine (BZB50E9QVY) ; Tyramine (X8ZC7V0OX3)
    Language English
    Publishing date 2017-05-29
    Publishing country England
    Document type Journal Article ; Validation Study
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2017.05.082
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3203: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Synthetic molecules for disruption of the MYC protein-protein interface.

    Jacob, Nicholas T / Miranda, Pedro O / Shirey, Ryan J / Gautam, Ritika / Zhou, Bin / de Orbe Izquierdo, M Elena / Hixon, Mark S / Hart, Jonathan R / Ueno, Lynn / Vogt, Peter K / Janda, Kim D

    Bioorganic & medicinal chemistry

    2018  Volume 26, Issue 14, Page(s) 4234–4239

    Abstract: MYC is a key transcriptional regulator involved in cellular proliferation and has established roles in transcriptional elongation and initiation, microRNA regulation, apoptosis, and pluripotency. Despite this prevalence, functional chemical probes of MYC ...

    Abstract MYC is a key transcriptional regulator involved in cellular proliferation and has established roles in transcriptional elongation and initiation, microRNA regulation, apoptosis, and pluripotency. Despite this prevalence, functional chemical probes of MYC function at the protein level have been limited. Previously, we discovered 5a, that binds to MYC with potency and specificity, downregulates the transcriptional activities of MYC and shows efficacy in vivo. However, this scaffold posed intrinsic pharmacokinetic liabilities, namely, poor solubility that precluded biophysical interrogation. Here, we developed a screening platform based on field-effect transistor analysis (Bio-FET), surface plasmon resonance (SPR), and a microtumor formation assay to analyze a series of new compounds aimed at improving these properties. This blind SAR campaign has produced a new lead compound of significantly increased in vivo stability and solubility for a 40-fold increase in exposure. This probe represents a significant advancement that will not only enable biophysical characterization of this interaction and further SAR, but also contribute to advances in understanding of MYC biology.
    MeSH term(s) Dose-Response Relationship, Drug ; Humans ; Hydrophobic and Hydrophilic Interactions ; Molecular Structure ; Protein Binding/drug effects ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/metabolism ; Pyridines/chemical synthesis ; Pyridines/chemistry ; Pyridines/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Solubility ; Structure-Activity Relationship ; Surface Plasmon Resonance
    Chemical Substances Proto-Oncogene Proteins c-myc ; Pyridines ; Pyrimidines ; pyrimidine (K8CXK5Q32L) ; pyridine (NH9L3PP67S)
    Language English
    Publishing date 2018-07-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2018.07.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3815: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma.

    Wang, Jun / Merino, Diana M / Light, Nicholas / Murphy, Brian L / Wang, Yong-Dong / Guo, Xiaohui / Hodges, Andrew P / Chau, Lianne Q / Liu, Kun-Wei / Dhall, Girish / Asgharzadeh, Shahab / Kiehna, Erin N / Shirey, Ryan J / Janda, Kim D / Taylor, Michael D / Malkin, David / Ellison, David W / VandenBerg, Scott R / Eberhart, Charles G /
    Sears, Rosalie C / Roussel, Martine F / Gilbertson, Richard J / Wechsler-Reya, Robert J

    Cancer research

    2019  Volume 79, Issue 9, Page(s) 2208–2219

    Abstract: Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms ... ...

    Abstract Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Carcinoma/drug therapy ; Carcinoma/genetics ; Carcinoma/pathology ; Choroid Plexus Neoplasms/drug therapy ; Choroid Plexus Neoplasms/genetics ; Choroid Plexus Neoplasms/pathology ; High-Throughput Screening Assays ; Mice ; Mice, Knockout ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Proto-Oncogene Proteins c-myc/physiology ; Small Molecule Libraries/pharmacology ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/physiology
    Chemical Substances Antineoplastic Agents ; Myc protein, mouse ; Proto-Oncogene Proteins c-myc ; Small Molecule Libraries ; Trp53 protein, mouse ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2019-03-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-18-2565
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.135/5: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top