| Literature DB >> 28002956 |
Stuart Jones, Jonathan Ahmet, Kelly Ayton, Matthew Ball1, Mark Cockerill, Emma Fairweather, Nicola Hamilton, Paul Harper, James Hitchin, Allan Jordan, Colin Levy1, Ruth Lopez1, Eddie McKenzie1, Martin Packer, Darren Plant, Iain Simpson, Peter Simpson, Ian Sinclair, Tim C P Somervaille, Helen Small, Gary J Spencer, Graeme Thomson, Michael Tonge, Ian Waddell, Jarrod Walsh, Bohdan Waszkowycz, Mark Wigglesworth, Daniel H Wiseman, Donald Ogilvie.
Abstract
A collaborative high throughput screen of 1.35 million compounds against mutant (R132H) isocitrate dehydrogenase IDH1 led to the identification of a novel series of inhibitors. Elucidation of the bound ligand crystal structure showed that the inhibitors exhibited a novel binding mode in a previously identified allosteric site of IDH1 (R132H). This information guided the optimization of the series yielding submicromolar enzyme inhibitors with promising cellular activity. Encouragingly, one compound from this series was found to induce myeloid differentiation in primary human IDH1 R132H AML cells in vitro.Entities:
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Year: 2016 PMID： 28002956 DOI： 10.1021/acs.jmedchem.6b01320
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446