TY - JOUR
T1 - Synthesis and Biological Investigation of (+)-JD1, an Organometallic BET Bromodomain Inhibitor
AU - Hassell-Hart, Storm
AU - Runcie, Andrew
AU - Krojer, Tobias
AU - Doyle, Jordan
AU - Lineham, Ella
AU - Ocasio, Cory A.
AU - Neto, Brenno A. D.
AU - Fedorov, Oleg
AU - Marsh, Graham
AU - Maple, Hannah
AU - Felix, Robert
AU - Banks, Rebecca
AU - Ciulli, Alessio
AU - Picaud, Sarah
AU - Filippakopoulos, Panagis
AU - Von Delft, Frank
AU - Brennan, Paul
AU - Stewart, Helen J. S.
AU - Chevassut, Timothy J.
AU - Walker, Martin
AU - Austin, Carol
AU - Morley, Simon
AU - Spencer, John
PY - 2020/2/10
Y1 - 2020/2/10
N2 - (+)-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.
AB - (+)-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.
UR - http://www.scopus.com/inward/record.url?scp=85077004008&partnerID=8YFLogxK
U2 - 10.1021/acs.organomet.9b00750
DO - 10.1021/acs.organomet.9b00750
M3 - Article
AN - SCOPUS:85077004008
VL - 39
JO - Organometallics
JF - Organometallics
SN - 0276-7333
IS - 3
ER -
