R
Real Denis
Researcher at Shire plc
Publications - 20
Citations - 1305
Real Denis is an academic researcher from Shire plc. The author has contributed to research in topics: Apoptosis & Structure–activity relationship. The author has an hindex of 11, co-authored 20 publications receiving 1220 citations.
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Journal ArticleDOI
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group.
William Kemnitzer,John Drewe,Songchun Jiang,Hong Zhang,Yan Wang,Jianghong Zhao,Shaojuan Jia,John Herich,Denis Labreque,Richard Storer,Karen Meerovitch,David Y. Bouffard,Rabindra Rej,Real Denis,Charles Blais,Serge Lamothe,Giorgio Attardo,Henriette Gourdeau,Ben Tseng,Shailaja Kasibhatla,Sui Xiong Cai +20 more
TL;DR: Results confirm that the cell-based caspase activation assay is a powerful tool for the discovery of potent apoptosis inducers and suggest that the 4-aryl-4H-chromenes have the potential to be developed into future anticancer agents.
Journal ArticleDOI
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure–activity relationships of the 7- and 5-, 6-, 8-positions
William Kemnitzer,Shailaja Kasibhatla,Songchun Jiang,Hong Zhang,Jianghong Zhao,Shaojuan Jia,Lifen Xu,Candace Crogan-Grundy,Real Denis,Nancy Barriault,Louis Vaillancourt,Sylvie Charron,Jennifer Dodd,Giorgio Attardo,Denis Labrecque,Serge Lamothe,Henriette Gourdeau,Ben Tseng,John Drewe,Sui Xiong Cai +19 more
TL;DR: It was found that a small hydrophobic group, such as NMe2, NH2, NHEt, and OMe, is preferred at the 7-position, and several 7-substituted and 7,8-di-subStituted analogs were found to have similar potencies as the lead compound MX58151 both as caspase activators and inhibitors of cell proliferation.
Journal ArticleDOI
Discovery of 4-Aryl-4H-chromenes as a New Series of Apoptosis Inducers Using a Cell- and Caspase-Based High Throughput Screening Assay. 4. Structure–Activity Relationships of N-Alkyl Substituted Pyrrole Fused at the 7,8-Positions
William Kemnitzer,John Drewe,Songchun Jiang,Hong Zhang,Candace Crogan-Grundy,Denis Labreque,Monica Bubenick,Giorgio Attardo,Real Denis,Serge Lamothe,Henriette Gourdeau,Ben Tseng,Shailaja Kasibhatla,Sui Xiong Cai +13 more
TL;DR: A methyl group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range and they inhibited tubulin polymerization, indicating that methylation of the7-position nitrogen does not change the mechanism of action of these chromenes.
Journal ArticleDOI
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions.
William Kemnitzer,John Drewe,Songchun Jiang,Hong Zhang,Jianghong Zhao,Candace Crogan-Grundy,Lifen Xu,Serge Lamothe,Henriette Gourdeau,Real Denis,Ben Tseng,Shailaja Kasibhatla,Sui Xiong Cai +12 more
TL;DR: The SAR of the 4-aryl group was found to be similar for chromenes with a fused ring at the 7,8-positions, and these compounds were found to inhibit tubulin polymerization, indicating that cyclization of the 6- or 7- positions into a ring does not change the mechanism of action.
Journal ArticleDOI
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based HTS assay. Part 5: modifications of the 2- and 3-positions.
William Kemnitzer,Songchun Jiang,Yan Wang,Shailaja Kasibhatla,Candace Crogan-Grundy,Monica Bubenik,Denis Labrecque,Real Denis,Serge Lamothe,Giorgio Attardo,Henriette Gourdeau,Ben Tseng,John Drewe,Sui Xiong Cai +13 more
TL;DR: The 2- H analog 3d was found to be much more stable under acidic conditions compared to the 2-NH(2) analog 3b, suggesting that 2-H analogs might have better bioavailability than the 2 -NH( 2) analogs.