dc.contributor.author | Kircher, Theresa | |
dc.contributor.author | Pantsar, Tatu | |
dc.contributor.author | Oder, Andreas | |
dc.contributor.author | Peter von Kries, Jens | |
dc.contributor.author | Juchum, Michael | |
dc.contributor.author | Pfaffenrot, Bent | |
dc.contributor.author | Kloevekorn, Philip | |
dc.contributor.author | Albrecht, Wolfgang | |
dc.contributor.author | Selig, Roland | |
dc.contributor.author | Laufer, Stefan | |
dc.date.accessioned | 2021-01-20T11:49:19Z | |
dc.date.available | 2021-01-20T11:49:19Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://erepo.uef.fi/handle/123456789/24271 | |
dc.description.abstract | The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in liver regeneration and is under investigation as a target for stimulating hepatocytes to increased proliferation. Therefore, new small molecules inhibiting MKK4 may represent a promising approach for treating acute and chronic liver diseases. Fluorescently labeled compounds are useful tools for high-throughput screenings of large compound libraries. Here we utilized the azaindole-based scaffold of FDA-approved BRAF inhibitor vemurafenib 1, which displays off-target activity on MKK4, as a starting point in our fluorescent compound design. Chemical variation of the scaffold and optimization led to a selection of fluorescent 5-TAMRA derivatives which possess high binding affinities on MKK4. Compound 45 represents a suitable tool compound for Fluorescence polarization assays to identify new small-molecule inhibitors of MKK4. | |
dc.language.iso | englanti | |
dc.publisher | Elsevier BV | |
dc.relation.ispartofseries | European journal of medicinal chemistry | |
dc.relation.uri | http://dx.doi.org/10.1016/j.ejmech.2020.112901 | |
dc.rights | CC BY-NC-ND 4.0 | |
dc.subject | mitogen-activated protein kinase kinase 4 | |
dc.subject | vemurafenib | |
dc.subject | fluorescence polarization assay | |
dc.title | Design and synthesis of novel fluorescently labeled analogs of vemurafenib targeting MKK4 | |
dc.description.version | final draft | |
dc.contributor.department | School of Pharmacy, Activities | |
uef.solecris.id | 74317836 | en |
dc.type.publication | Tieteelliset aikakauslehtiartikkelit | |
dc.relation.doi | 10.1016/j.ejmech.2020.112901 | |
dc.description.reviewstatus | peerReviewed | |
dc.publisher.country | Ranska | |
dc.relation.articlenumber | 112901 | |
dc.relation.issn | 0223-5234 | |
dc.relation.volume | 209 | |
dc.rights.accesslevel | openAccess | |
dc.type.okm | A1 | |
uef.solecris.openaccess | Ei | |
dc.rights.copyright | © 2020 Elsevier Masson SAS. | |
dc.type.displayType | article | en |
dc.type.displayType | artikkeli | fi |
dc.rights.url | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |