Jen Macaluso
4 Papers
59 Citations
Jen Macaluso is an academic researcher. The author has contributed to research in topics: Bruton's tyrosine kinase & Chemistry. The author has an hindex of 3, co-authored 3 publications.
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Papers
Potent and selective Bruton's tyrosine kinase inhibitors: Discovery of GDC-0834.
Wendy B. Young,James Barbosa,Peter Blomgren,Meire Bremer,James J. Crawford,Donna Dambach,Steve Gallion,Sarah G. Hymowitz,Kropf Jeffrey E,Seung H. Lee,Lichuan Liu,Joseph W. Lubach,Jen Macaluso,Pat Maciejewski,Brigitte Maurer,Scott A. Mitchell,Daniel F. Ortwine,Julie Di Paolo,Karin Reif,Heleen Scheerens,Aaron C. Schmitt,C. Gregory Sowell,Xiaojing Wang,Harvey Wong,Jin-Ming Xiong,Jianjun Xu,Zhongdong Zhao,Kevin S. Currie +27 more
TL;DR: In human, 2 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure, which informed the back-up program and discovery of improved inhibitors.
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Discovery of Potent and Selective Tricyclic Inhibitors of Bruton’s Tyrosine Kinase with Improved Druglike Properties
Xiaojing Wang,James Barbosa,Peter Blomgren,Meire Bremer,Jacob Z. Chen,James J. Crawford,Wei Deng,Liming Dong,Charles Eigenbrot,Steve Gallion,Jonathon Hau,Huiyong Hu,Adam R. Johnson,Arna Katewa,Kropf Jeffrey E,Seung H. Lee,Lichuan Liu,Joseph W. Lubach,Jen Macaluso,Pat Maciejewski,Scott A. Mitchell,Daniel F. Ortwine,Julie DiPaolo,Karin Reif,Heleen Scheerens,Aaron C. Schmitt,Harvey Wong,Jin-Ming Xiong,Jianjun Xu,Zhongdong Zhao,Fusheng Zhou,Kevin S. Currie,Wendy B. Young +32 more
TL;DR: A series of novel tricyclic compounds that improved upon the druglike properties of previous chemical matter are devised that are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.
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Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively
Kanak Raina,C.D. Forbes,Rebecca Stronk,Jonathan P. Rappi,Kyle J. Eastman,Samuel Gerritz,Xinheng Yu,Hao Li,Amit Bhardwaj,Mia E. Forgione,Abigail Hundt,Madeline P. King,Zoe M. Posner,Allison Denny,Andrew McGovern,David E. Puleo,Ethan Garvin,Rebekka Chenard,Nilesh Zaware,James J. Mousseau,Jen Macaluso,Michael Martin,Kyle Bassoli,Kelli Jones,Marco Garcia,K. Howard,Levi M. Smith,Jinshan Chen,Cesar A. De Leon,John Hines,Katherine J. Kayser-Bricker,Craig M. Crews +31 more
TL;DR: In this article , the authors describe a proof-of-concept study using novel heterobifunctional small molecules called Regulated Induced Proximity Targeting Chimeras or RIPTACs, which elicit a stable ternary complex between a target protein selectively expressed in cancer tissue and a pan-expressed protein essential for cell survival.
Discovery of highly potent and selective Bruton's tyrosine kinase inhibitors: Pyridazinone analogs with improved metabolic stability.
Wendy B. Young,James Barbosa,Peter Blomgren,Meire Bremer,James J. Crawford,Donna Dambach,Charles Eigenbrot,Steve Gallion,Adam R. Johnson,Kropf Jeffrey E,Seung H. Lee,Lichuan Liu,Joseph W. Lubach,Jen Macaluso,Pat Maciejewski,Scott A. Mitchell,Daniel F. Ortwine,Julie Di Paolo,Karin Reif,Heleen Scheerens,Aaron C. Schmitt,Xiaojing Wang,Harvey Wong,Jin-Ming Xiong,Jianjun Xu,Christine Yu,Zhongdong Zhao,Kevin S. Currie +27 more
TL;DR: SAR studies were focused on reducing metabolic cleavage of this amide, and resulted in the identification of several central aryl linker substituents that conferred improved stability and preclinical properties.