Borrello, T;
Tam, CH;
Shafat, M;
Rushworth, S;
Bowles, K;
Bailey, S;
Crabb, S;
... Douglas, L; + view all
(2020)
Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML.
ChemRxiv: Cambridge, UK.
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Abstract
Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues containing a carboxamide at the 4-position of the aryl ring and novel carbamates. These compounds were potent submicromolar LSD1 inhibitors in enzyme assays and were anti-proliferative against a panel of AML cell lines. LSD1 target engagement in cells was demonstrated through the effects on H3K4me2 protein expression, CD86, CD11b and CD14 levels.
| Type: | Working / discussion paper |
|---|---|
| Title: | Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.26434/chemrxiv.11860824.v1 |
| Publisher version: | https://doi.org/10.26434/chemrxiv.11860824.v1 |
| Language: | English |
| Additional information: | The content is available under CC BY NC ND 4.0 License (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| 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 Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10124446 |
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