Towards the development of chromone-based MEK1/2 modulators

Redwan, Itedale Namro, 1981 (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

Dyrager, Christine, 1975 (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

Solano, Carlos (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

de Trocóniz, Guillermo Fernández (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

Voisin, L. (author)

Bliman, David (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

Meloche, S. (author)

Grøtli, Morten, 1966 (author): Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology

(creator_code:org_t)

Elsevier BV, 2014
2014
English.
In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234. ; 85, s. 127-138

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

Inhibition or allosteric modulation of mitogen-activated protein kinase kinases MEK1 and MEK2 (MEK1/2) represent a promising strategy for the discovery of new specific anticancer agents. In this paper, structure-based design, beginning from the lead compound PD98059, was used to study potential structural modifications on the chromone structure in order to obtain highly potent derivatives that target the allosteric pocket in MEK1. Subsequently, a small series of PD98059 analogs were synthesized to provide a first generation of chromone-based derivatives that inhibit the activation of MEK1 with IC50 values as low as 30 nM in vitro. Complementary cellular studies also showed that two of the compounds in the series inhibit the activity of MEK1/2 with IC50 values in the nanomolar range (73-97 nM). In addition, compounds in this series were found to inhibit the proliferation of a small panel of human cancer cell lines.

By the author/editor: Redwan, Itedale ...; Dyrager, Christi ...; Solano, Carlos; de Trocóniz, Gui ...; Voisin, L.; Bliman, David; show more...; Meloche, S.; Grøtli, Morten, ...; show less...

About the subject

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.