LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 38

Search options

  1. Article ; Online: The experiment is the limit.

    Schindler, Christina E M / Kuhn, Daniel / Hartung, Ingo V

    Nature reviews. Chemistry

    2023  Volume 7, Issue 11, Page(s) 752–753

    Language English
    Publishing date 2023-10-23
    Publishing country England
    Document type Journal Article
    ISSN 2397-3358
    ISSN (online) 2397-3358
    DOI 10.1038/s41570-023-00552-4
    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: No shortcuts to SARS-CoV-2 antivirals.

    Edwards, Aled / Hartung, Ingo V

    Science (New York, N.Y.)

    2021  Volume 373, Issue 6554, Page(s) 488–489

    MeSH term(s) Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19 ; Humans ; SARS-CoV-2 ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2021-07-29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abj9488
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 27: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 77: Show issues

    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: Rules were made to be broken.

    Hartung, Ingo V / Huck, Bayard R / Crespo, Alejandro

    Nature reviews. Chemistry

    2022  Volume 7, Issue 1, Page(s) 3–4

    Language English
    Publishing date 2022-02-17
    Publishing country England
    Document type Journal Article
    ISSN 2397-3358
    ISSN (online) 2397-3358
    DOI 10.1038/s41570-022-00451-0
    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: Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.

    Hartung, Ingo V / Rudolph, Joachim / Mader, Mary M / Mulder, Monique P C / Workman, Paul

    Journal of medicinal chemistry

    2023  Volume 66, Issue 14, Page(s) 9297–9312

    Abstract: Within druggable target space, new small-molecule modalities, particularly covalent inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists. Molecules with such modes of action have a large potential not only as drugs but ... ...

    Abstract Within druggable target space, new small-molecule modalities, particularly covalent inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists. Molecules with such modes of action have a large potential not only as drugs but also as chemical probes. Criteria have previously been established to describe the potency, selectivity, and properties of small-molecule probes that are qualified to enable the interrogation and validation of drug targets. These definitions have been tailored to reversibly acting modulators but fall short in their applicability to other modalities. While initial guidelines have been proposed, we delineate here a full set of criteria for the characterization of covalent, irreversible inhibitors as well as heterobifunctional degraders ("proteolysis-targeting chimeras", or PROTACs) and molecular glue degraders. We propose modified potency and selectivity criteria compared to those for reversible inhibitors. We discuss their relevance and highlight examples of suitable probe and pathfinder compounds.
    MeSH term(s) Proteolysis ; Ubiquitin-Protein Ligases
    Chemical Substances Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2023-07-05
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00550
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: 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)
    Zs.MB 1: Show issues

    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: Which Small Molecule? Selecting Chemical Probes for Use in Cancer Research and Target Validation.

    Mader, Mary M / Rudolph, Joachim / Hartung, Ingo V / Uehling, David / Workman, Paul / Zuercher, William

    Cancer discovery

    2023  Volume 13, Issue 10, Page(s) 2150–2165

    Abstract: Small-molecule chemical "probes" complement the use of molecular biology techniques to explore, validate, and generate hypotheses on the function of proteins in diseases such as cancer. Unfortunately, the poor selection and use of small-molecule reagents ...

    Abstract Small-molecule chemical "probes" complement the use of molecular biology techniques to explore, validate, and generate hypotheses on the function of proteins in diseases such as cancer. Unfortunately, the poor selection and use of small-molecule reagents can lead to incorrect conclusions. Here, we illustrate examples of poor chemical tools and suggest best practices for the selection, validation, and use of high-quality chemical probes in cancer research. We also note the complexity associated with tools for novel drug modalities, exemplified by protein degraders, and provide advice and resources to facilitate the independent identification of appropriate small-molecule probes by researchers.
    Significance: Validation of biological targets and pathways will be aided by a shared understanding of the criteria of potency, selectivity, and target engagement associated with small-molecule reagents ("chemical probes") that enable that work. Interdisciplinary collaboration between cancer biologists, medicinal chemists, and chemical biologists and the awareness of available resources will reduce misleading data generation and interpretation, strengthen data robustness, and improve productivity in academic and industrial research.
    MeSH term(s) Humans ; Research ; Proteins ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances Proteins
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-23-0536
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6916: 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.

  6. Article ; Online: The 17

    Ciulli, Alessio / O'Connor, Suzanne / Chung, Chun-Wa / Hartung, Ingo V / Testa, Andrea / Daniels, Danette L / Heitman, Laura H

    ChemMedChem

    2023  Volume 18, Issue 20, Page(s) e202300464

    Abstract: ... The ... ...

    Abstract The 17
    MeSH term(s) Chemistry, Pharmaceutical ; Drug Design ; Europe ; Proteolysis ; South Africa
    Language English
    Publishing date 2023-10-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2218496-X
    ISSN 1860-7187 ; 1860-7179
    ISSN (online) 1860-7187
    ISSN 1860-7179
    DOI 10.1002/cmdc.202300464
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6280: 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.

  7. Article ; Online: A miniaturized mode-of-action profiling platform enables high throughput characterization of the molecular and cellular dynamics of EZH2 inhibition.

    Falkenstern, Lilia / Georgi, Victoria / Bunse, Stefanie / Badock, Volker / Husemann, Manfred / Roehn, Ulrike / Stellfeld, Timo / Fitzgerald, Mark / Ferrara, Steven / Stöckigt, Detlef / Stresemann, Carlo / Hartung, Ingo V / Fernández-Montalván, Amaury

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 1739

    Abstract: The market approval of Tazemetostat (TAZVERIK) for the treatment of follicular lymphoma and epithelioid sarcoma has established "enhancer of zeste homolog 2" (EZH2) as therapeutic target in oncology. Despite their structural similarities and common mode ... ...

    Abstract The market approval of Tazemetostat (TAZVERIK) for the treatment of follicular lymphoma and epithelioid sarcoma has established "enhancer of zeste homolog 2" (EZH2) as therapeutic target in oncology. Despite their structural similarities and common mode of inhibition, Tazemetostat and other EZH2 inhibitors display differentiated pharmacological profiles based on their target residence time. Here we established high throughput screening methods based on time-resolved fluorescence energy transfer, scintillation proximity and high content analysis microscopy to quantify the biochemical and cellular binding of a chemically diverse collection of EZH2 inhibitors. These assays allowed to further characterize the interplay between EZH2 allosteric modulation by methylated histone tails (H3K27me3) and inhibitor binding, and to evaluate the impact of EZH2's clinically relevant mutant Y641N on drug target residence times. While all compounds in this study exhibited slower off-rates, those with clinical candidate status display significantly slower target residence times in wild type EZH2 and disease-related mutants. These inhibitors interact in a more entropy-driven fashion and show the most persistent effects in cellular washout and antiproliferative efficacy experiments. Our work provides mechanistic insights for the largest cohort of EZH2 inhibitors reported to date, demonstrating that-among several other binding parameters-target residence time is the best predictor of cellular efficacy.
    MeSH term(s) Humans ; Benzamides ; Biphenyl Compounds ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Morpholines ; Pyridones/therapeutic use
    Chemical Substances Benzamides ; Biphenyl Compounds ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Enzyme Inhibitors ; EZH2 protein, human (EC 2.1.1.43) ; Morpholines ; Pyridones ; tazemetostat (Q40W93WPE1)
    Language English
    Publishing date 2024-01-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-50964-x
    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.

  8. Article ; Online: The European Federation for Medicinal Chemistry and Chemical Biology (EFMC) Best Practice Initiative: Hit Generation.

    Quancard, Jean / Vulpetti, Anna / Bach, Anders / Cox, Brian / Guéret, Stéphanie M / Hartung, Ingo V / Koolman, Hannes F / Laufer, Stefan / Messinger, Josef / Sbardella, Gianluca / Craft, Russell

    ChemMedChem

    2023  Volume 18, Issue 9, Page(s) e202300002

    Abstract: Hit generation is a crucial step in drug discovery that will determine the speed and chance of success of identifying drug candidates. Many strategies are now available to identify chemical starting points, or hits, and each biological target warrants a ... ...

    Abstract Hit generation is a crucial step in drug discovery that will determine the speed and chance of success of identifying drug candidates. Many strategies are now available to identify chemical starting points, or hits, and each biological target warrants a tailored approach. In this set of best practices, we detail the essential approaches for target centric hit generation and the opportunities and challenges they come with. We then provide guidance on how to validate hits to ensure medicinal chemistry is only performed on compounds and scaffolds that engage the target of interest and have the desired mode of action. Finally, we discuss the design of integrated hit generation strategies that combine several approaches to maximize the chance of identifying high quality starting points to ensure a successful drug discovery campaign.
    MeSH term(s) Chemistry, Pharmaceutical ; Drug Discovery ; Biology
    Language English
    Publishing date 2023-03-09
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2218496-X
    ISSN 1860-7187 ; 1860-7179
    ISSN (online) 1860-7187
    ISSN 1860-7179
    DOI 10.1002/cmdc.202300002
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6280: 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.

  9. Article ; Online: Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.

    Krieger, Johannes / Sorrell, Fiona J / Wegener, Ansgar A / Leuthner, Birgitta / Machrouhi-Porcher, Fouzia / Hecht, Martin / Leibrock, Eva M / Müller, Juliane E / Eisert, Jonathan / Hartung, Ingo V / Schlesiger, Sarah

    ChemMedChem

    2023  Volume 18, Issue 8, Page(s) e202200615

    Abstract: Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data ... ...

    Abstract Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data set which allows for direct comparison of structural variations including those which were so far hidden in patent literature. The gained knowledge about improved VHL binders was used to design a small library of highly potent BRD4-degraders comprising different VHL exit vectors. Newly designed degraders showed favorable molecular properties and significantly improved degradation potency compared to MZ1.
    MeSH term(s) Von Hippel-Lindau Tumor Suppressor Protein/metabolism ; Ligands ; Nuclear Proteins/metabolism ; Proteolysis ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27) ; Ligands ; Nuclear Proteins ; Transcription Factors ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2023-02-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2218496-X
    ISSN 1860-7187 ; 1860-7179
    ISSN (online) 1860-7187
    ISSN 1860-7179
    DOI 10.1002/cmdc.202200615
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6280: 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.

  10. Article ; Online: Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY-747 designed for the treatment of resistant hypertension.

    Wunder, Frank / Stasch, Johannes-Peter / Knorr, Andreas / Mondritzki, Thomas / Brockschnieder, Damian / Becker-Pelster, Eva-Maria / Sandner, Peter / Tinel, Hanna / Redlich, Gorden / Hartung, Ingo V / Vakalopoulos, Alexandros / Follmann, Markus

    British journal of pharmacology

    2023  Volume 180, Issue 19, Page(s) 2500–2513

    Abstract: Background and purpose: First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC ... ...

    Abstract Background and purpose: First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required.
    Experimental approach: We report the high-throughput screening (HTS)-based discovery of a second generation of sGC stimulators from a novel imidazo[1,2-a]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY-747). The pharmacokinetic profile of BAY-747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension.
    Key results: BAY-747 is a highly potent sGC stimulator in vitro. In addition, BAY-747 showed an excellent pharmacokinetic profile with long half-life and low peak-to-trough ratio. BAY-747 was investigated in experimental in vivo models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY-747 caused a dose-related and long-lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12 days resulted in a persistent decrease. BAY-747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY-747 caused a dose-related and long-lasting (>6 h) MAP decrease.
    Conclusion and implications: BAY-747 is a potent, orally available sGC stimulator. BAY-747 shows long-acting pharmacodynamic effects with a very low peak-to-trough ratio. BAY-747 could be a treatment alternative for patients with hypertension, especially those not responding to standard-of-care therapy.
    MeSH term(s) Rats ; Animals ; Dogs ; Soluble Guanylyl Cyclase ; Hypertension/drug therapy ; Hypertension, Pulmonary/drug therapy ; Heart Failure/drug therapy ; Vasodilator Agents/therapeutic use
    Chemical Substances Soluble Guanylyl Cyclase (EC 4.6.1.2) ; 2-(2-Chloro-4-(methylsulfonyl)-3-((2,2,2-trifluoroethoxy)methyl)benzoyl)-1,3-cyclohexanedione (BAY 747) ; Vasodilator Agents
    Language English
    Publishing date 2023-06-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16142
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uf I Zs.146: 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