Speranzini, V;
Rotili, D;
Ciossani, G;
Pilotto, S;
Marrocco, B;
Forgione, M;
Lucidi, A;
... Mattevi, A; + view all
(2016)
Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features.
Science Advances
, 2
(9)
, Article e1601017. 10.1126/sciadv.1601017.
Preview |
Text
Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features.pdf - Published Version Download (702kB) | Preview |
Abstract
Because of its involvement in the progression of several malignant tumors, the histone lysine-specific demethylase 1 (LSD1) has become a prominent drug target in modern medicinal chemistry research. We report on the discovery of two classes of noncovalent inhibitors displaying unique structural features. The antibiotics polymyxins bind at the entrance of the substrate cleft, where their highly charged cyclic moiety interacts with a cluster of positively charged amino acids. The same site is occupied by quinazoline-based compounds, which were found to inhibit the enzyme through a most peculiar mode because they form a pile of five to seven molecules that obstruct access to the active center. These data significantly indicate unpredictable strategies for the development of epigenetic inhibitors.
| Type: | Article |
|---|---|
| Title: | Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.1601017 |
| Publisher version: | https://doi.org/10.1126/sciadv.1601017 |
| Language: | English |
| Additional information: | 2016 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, HISTONE DEMETHYLASE LSD1, BINDING, PROTEIN, RECOGNITION, METHYLTRANSFERASE, DERIVATIVES, CANCER, CELLS, TRANS-2-PHENYLCYCLOPROPYLAMINE, DIFFERENTIATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057106 |
Archive Staff Only
 |
View Item |
