Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor
(+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was dete...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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American Chemical Society
2019
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| _version_ | 1826259065403080704 |
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| author | Hassell-Hart, S Runcie, A Krojer, T Doyle, J Lineham, E Ocasio, CA Neto, BAD Fedorov, O Marsh, G Maple, H Felix, R Banks, R Ciulli, A Picaud, S Filippakopoulos, P von Delft, F Brennan, P Stewart, HJS Chevassut, TJ Walker, M Austin, C Morley, S Spencer, J |
| author_facet | Hassell-Hart, S Runcie, A Krojer, T Doyle, J Lineham, E Ocasio, CA Neto, BAD Fedorov, O Marsh, G Maple, H Felix, R Banks, R Ciulli, A Picaud, S Filippakopoulos, P von Delft, F Brennan, P Stewart, HJS Chevassut, TJ Walker, M Austin, C Morley, S Spencer, J |
| author_sort | Hassell-Hart, S |
| collection | OXFORD |
| description | (+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4. |
| first_indexed | 2024-03-06T18:43:59Z |
| format | Journal article |
| id | oxford-uuid:0dddd75d-2955-40bc-a536-0183f715c588 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:43:59Z |
| publishDate | 2019 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:0dddd75d-2955-40bc-a536-0183f715c5882022-03-26T09:42:50ZSynthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitorJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0dddd75d-2955-40bc-a536-0183f715c588Symplectic Elements at OxfordAmerican Chemical Society2019Hassell-Hart, SRuncie, AKrojer, TDoyle, JLineham, EOcasio, CANeto, BADFedorov, OMarsh, GMaple, HFelix, RBanks, RCiulli, APicaud, SFilippakopoulos, Pvon Delft, FBrennan, PStewart, HJSChevassut, TJWalker, MAustin, CMorley, SSpencer, J(+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4. |
| spellingShingle | Hassell-Hart, S Runcie, A Krojer, T Doyle, J Lineham, E Ocasio, CA Neto, BAD Fedorov, O Marsh, G Maple, H Felix, R Banks, R Ciulli, A Picaud, S Filippakopoulos, P von Delft, F Brennan, P Stewart, HJS Chevassut, TJ Walker, M Austin, C Morley, S Spencer, J Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title | Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title_full | Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title_fullStr | Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title_full_unstemmed | Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title_short | Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor |
| title_sort | synthesis and biological investigation of jd1 an organometallic bet bromodomain inhibitor |
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