All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

An identification of MARK inhibitors using high throughput MALDI-TOF mass spectrometry

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73612578" target="_blank" >RIV/61989592:15110/22:73612578 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S0753332221013366?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0753332221013366?via%3Dihub</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.biopha.2021.112549" target="_blank" >10.1016/j.biopha.2021.112549</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    An identification of MARK inhibitors using high throughput MALDI-TOF mass spectrometry

  • Original language description

    MAP/micmtubule affinity-regulating kinases (MARKs) were recently identified as potential drug targets for Alzheimer&apos;s disease (AD) due to their role in pathological hyperphosphorylation of tau protein. Hyperphosphorylated tau has decreased affinity for microtubule binding, impairing their stability and associated functions. Destabilization of microtubules in neuronal cells leads to neumdegeneration, and microtubuleunbound tau forms neurofibrillary tangles, one of the primary hallmarks of AD. Many phosphorylation sites of tau protein have been identified, but phosphorylation at Ser(262) , which occurs in early stages of AD, plays a vital role in the pathological hyperphosphorylation of tau. It has been found that Ser(262) is phosphorylated by MARK4, which is currently an intensively studied target for treating Alzheimer&apos;s disease and other neurodegenerative diseases. Our present study aimed to develop a high throughput compatible assay to directly detect MARK enzymatic activity using echoacoustic transfer and MALDI-TOF mass spectrometer. We optimized the assay for all four isoforms of MARK and validated its use for identifying potential inhibitors by the screening of 1280 compounds from the LOPAC (R) 1280 International (Library Of Pharmacologically Active Compounds). Six MARK4 inhibitors with IC50 &lt; 1 mu M were identified. To demonstrate their therapeutic potential, active compounds were further tested for MARK4 selectivity and ability to cross the blood-brain barrier. Lastly, the molecular docking with the most active inhibitors to predict their interaction with MARK4 was performed.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    BIOMEDICINE &amp; PHARMACOTHERAPY

  • ISSN

    0753-3322

  • e-ISSN

    1950-6007

  • Volume of the periodical

    146

  • Issue of the periodical within the volume

    February 2022

  • Country of publishing house

    FR - FRANCE

  • Number of pages

    10

  • Pages from-to

    112549

  • UT code for WoS article

    000744602000002

  • EID of the result in the Scopus database

    2-s2.0-85121204355