16671-66-2Relevant articles and documents
Discovery of an MLLT1/3 YEATS Domain Chemical Probe
Moustakim, Moses,Christott, Thomas,Monteiro, Octovia P.,Bennett, James,Giroud, Charline,Ward, Jennifer,Rogers, Catherine M.,Smith, Paul,Panagakou, Ioanna,Díaz-Sáez, Laura,Felce, Suet Ling,Gamble, Vicki,Gileadi, Carina,Halidi, Nadia,Heidenreich, David,Chaikuad, Apirat,Knapp, Stefan,Huber, Kilian V. M.,Farnie, Gillian,Heer, Jag,Manevski, Nenad,Poda, Gennady,Al-awar, Rima,Dixon, Darren J.,Brennan, Paul E.,Fedorov, Oleg
supporting information, p. 16302 - 16307 (2018/11/23)
YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation of these modified lysine-binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterisation of the first small-molecule chemical probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3–histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed. Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small-molecule X-ray co-crystal structures with the MLLT1 YD are also reported. This first-in-class probe molecule can be used to understand MLLT1/3-associated biology and the therapeutic potential of small-molecule YD inhibitors.
