FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2297267199> ?p ?o ?g. }

• W2297267199 abstract "Aberrant production of proinflammatory cytokines is linked to many autoimmune diseases, and their inhibition by small molecule compounds is considered beneficial. Here, we performed phenotypic screening in IFNγ/LPS-activated RAW264.7, mouse macrophage cells, and discovered AS2677131 and AS2795440 as novel and potent inhibitors of IL-12p40, a subunit of IL-23. Interestingly, these compounds exhibited unique pharmacological activities in their inhibition of the production of IL-12p40, IL-6 and IL-1β but not TNFα in activated macrophages or dendritic cells, and expression of IgM-induced MHC class II on B cells. To reveal these mechanisms, we synthesized two different activity probes which were structurally related to the AS compounds, and identified probe-specific binding proteins, including PIKfyve, a Class III PI kinase. The AS compounds inhibited PIKfyve activity and mimicked the properties of PIKfyve-deficient cells, eventually validating PIKfyve as target molecule. Regarding mechanism, AS2677131 regulated DNA binding activity of c-Rel on IL-12p40 and IL-1β promoter. As expected, a PIKfyve inhibitor prevented the development of arthritis in rats. Taken together, our findings of the novel and potent PIKfyve inhibitors AS2677131 and AS2795440 reveal the critical role of PIKfyve in proinflammatory cytokine production and B cell activation, and may indicate a potential new therapeutic option for treatment of inflammatory diseases." @default.
• W2297267199 created "2016-06-24" @default.
• W2297267199 creator A5025165711 @default.
• W2297267199 creator A5025625167 @default.
• W2297267199 creator A5036387418 @default.
• W2297267199 creator A5038373924 @default.
• W2297267199 creator A5038831866 @default.
• W2297267199 creator A5054760830 @default.
• W2297267199 creator A5058132787 @default.
• W2297267199 creator A5066893619 @default.
• W2297267199 creator A5074152292 @default.
• W2297267199 creator A5076280774 @default.
• W2297267199 date "2016-06-01" @default.
• W2297267199 modified "2023-09-26" @default.
• W2297267199 title "Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor" @default.
• W2297267199 cites W1904705252 @default.
• W2297267199 cites W1946164369 @default.
• W2297267199 cites W1966999437 @default.
• W2297267199 cites W1973661706 @default.
• W2297267199 cites W1981489800 @default.
• W2297267199 cites W1989283034 @default.
• W2297267199 cites W1998103686 @default.
• W2297267199 cites W2001323513 @default.
• W2297267199 cites W2001617137 @default.
• W2297267199 cites W2003236418 @default.
• W2297267199 cites W2012228539 @default.
• W2297267199 cites W2022104546 @default.
• W2297267199 cites W2022244055 @default.
• W2297267199 cites W2023410461 @default.
• W2297267199 cites W2031071878 @default.
• W2297267199 cites W2034320996 @default.
• W2297267199 cites W2036539000 @default.
• W2297267199 cites W2037127114 @default.
• W2297267199 cites W2042166751 @default.
• W2297267199 cites W2046969024 @default.
• W2297267199 cites W2052894538 @default.
• W2297267199 cites W2072270184 @default.
• W2297267199 cites W2083634877 @default.
• W2297267199 cites W2108263552 @default.
• W2297267199 cites W2116828514 @default.
• W2297267199 cites W2117262983 @default.
• W2297267199 cites W2118278336 @default.
• W2297267199 cites W2121874550 @default.
• W2297267199 cites W2122991277 @default.
• W2297267199 cites W2130933356 @default.
• W2297267199 cites W2133657961 @default.
• W2297267199 cites W2138018530 @default.
• W2297267199 cites W2139783156 @default.
• W2297267199 cites W2142446767 @default.
• W2297267199 cites W2146336227 @default.
• W2297267199 cites W81528658 @default.
• W2297267199 doi "https://doi.org/10.1016/j.ejphar.2016.03.036" @default.
• W2297267199 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27001378" @default.
• W2297267199 hasPublicationYear "2016" @default.
• W2297267199 type Work @default.
• W2297267199 sameAs 2297267199 @default.
• W2297267199 citedByCount "9" @default.
• W2297267199 countsByYear W22972671992017 @default.
• W2297267199 countsByYear W22972671992018 @default.
• W2297267199 countsByYear W22972671992019 @default.
• W2297267199 countsByYear W22972671992020 @default.
• W2297267199 countsByYear W22972671992021 @default.
• W2297267199 crossrefType "journal-article" @default.
• W2297267199 hasAuthorship W2297267199A5025165711 @default.
• W2297267199 hasAuthorship W2297267199A5025625167 @default.
• W2297267199 hasAuthorship W2297267199A5036387418 @default.
• W2297267199 hasAuthorship W2297267199A5038373924 @default.
• W2297267199 hasAuthorship W2297267199A5038831866 @default.
• W2297267199 hasAuthorship W2297267199A5054760830 @default.
• W2297267199 hasAuthorship W2297267199A5058132787 @default.
• W2297267199 hasAuthorship W2297267199A5066893619 @default.
• W2297267199 hasAuthorship W2297267199A5074152292 @default.
• W2297267199 hasAuthorship W2297267199A5076280774 @default.
• W2297267199 hasConcept C164027704 @default.
• W2297267199 hasConcept C203014093 @default.
• W2297267199 hasConcept C2776914184 @default.
• W2297267199 hasConcept C2778690821 @default.
• W2297267199 hasConcept C86803240 @default.
• W2297267199 hasConcept C95444343 @default.
• W2297267199 hasConceptScore W2297267199C164027704 @default.
• W2297267199 hasConceptScore W2297267199C203014093 @default.
• W2297267199 hasConceptScore W2297267199C2776914184 @default.
• W2297267199 hasConceptScore W2297267199C2778690821 @default.
• W2297267199 hasConceptScore W2297267199C86803240 @default.
• W2297267199 hasConceptScore W2297267199C95444343 @default.
• W2297267199 hasFunder F4320308747 @default.
• W2297267199 hasLocation W22972671991 @default.
• W2297267199 hasLocation W22972671992 @default.
• W2297267199 hasOpenAccess W2297267199 @default.
• W2297267199 hasPrimaryLocation W22972671991 @default.
• W2297267199 hasRelatedWork W1978281312 @default.
• W2297267199 hasRelatedWork W2010276207 @default.
• W2297267199 hasRelatedWork W2048489884 @default.
• W2297267199 hasRelatedWork W2064650401 @default.
• W2297267199 hasRelatedWork W2075067683 @default.
• W2297267199 hasRelatedWork W2083841175 @default.
• W2297267199 hasRelatedWork W2095588155 @default.
• W2297267199 hasRelatedWork W2167187046 @default.
• W2297267199 hasRelatedWork W2409435197 @default.
• W2297267199 hasRelatedWork W2184089562 @default.

• next