Zobrazeno 1 - 10
of 16
pro vyhledávání: '"Victor S. Gehling"'
Autor:
Venita G. Watson, Richard T. Cummings, Victor S. Gehling, Andrew C. Good, Brian K. Albrecht, Priyanka Sawant, John P. McGrath, James E. Audia, Jean-Christophe Harmange, Priyadarshini Iyer, Rishi G. Vaswani, Srividya Balasubramanian, Alexandre Côté, Avinash Khanna, Steven Bellon, Francois Brucelle, Julian Levell, Patrick Trojer, Jacob I. Stuckey, Martin Duplessis
Publikováno v:
ACS Med Chem Lett
[Image: see text] Leveraging the catalytic machinery of LSD1 (KDM1A), a series of covalent styrenylcyclopropane LSD1 inhibitors were identified. These inhibitors represent a new class of mechanism-based inhibitors that target and covalently label the
Autor:
Yichin Liu, Peter S. Dragovich, Daniel F. Ortwine, Birong Zhang, Richard D. Cummings, Jun Liang, Yingqing Ran, Marie Classon, Sharada Labadie, Tommy Lai, Weifeng Mao, Victor S. Gehling, Bianca M. Liederer, Erica Van der Porten, Jean-Christophe Harmange, Till Mauer, Le An, Xiaoping Zheng, Jiangpeng Liao, James R. Kiefer, Maia Vinogradova, Snahel Patel, Patrick Trojer, Gauri Deshmukh, Amy Gustafson, Lesley J. Murray
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 27:2974-2981
A high-throughput screening (HTS) of the Genentech/Roche library identified a novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding mode, initial attempts to improve inhibitor potency failed to improve potency, and synthesi
Autor:
Valérie Vivat, Patrick Trojer, Jehrod Burnett Brenneman, James E. Audia, Jennifer A. Mertz, Victor S. Gehling, Shilpi Arora, Ashwin Ramakrishnan, Richard T. Cummings, Ludivine Moine, Jacob I. Stuckey, Robert J. Sims, Nico Cantone, Alexandre Côté, Avinash Khanna, Julian Levell
Publikováno v:
The Journal of Biological Chemistry
The histone methyltransferase EZH2 has been the target of numerous small-molecule inhibitor discovery efforts over the last 10+ years. Emerging clinical data have provided early evidence for single agent activity with acceptable safety profiles for f
Autor:
Srividya Balasubramanian, Robert K. Campbell, Patrick Trojer, Christina O. Lee, Jon R. Wilson, Emmanuel Normant, Les A. Dakin, Martin Duplessis, Brian K. Albrecht, Jean-Christophe Harmange, Rishi G. Vaswani, James E. Audia, Priyadarshini Iyer, Andrew Simon Cook, Neil Justin, Steven J. Gamblin, Nico Cantone, Andrew C. Good, Feng Zhao, Richard T. Cummings, Steven F. Bellon, Christopher G. Nasveschuk, Shuyang Chen, Ying Zhang, Victor S. Gehling
Publikováno v:
Journal of Medicinal Chemistry. 59:9928-9941
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prog
Autor:
Yichin Liu, Xiaoping Zheng, Lesley J. Murray, Marie Classon, Birong Zhang, Erica Van der Porten, Amy Gustafson, Jiangpeng Liao, Maia Vinogradova, Jean-Christophe Harmange, Weifeng Mao, Bianca M. Liederer, Tommy Lai, Sharada Labadie, Patrick Trojer, Richard D. Cummings, Victor S. Gehling, Gauri Deshmukh, James R. Kiefer, Peter S. Dragovich, Daniel F. Ortwine, Jun Liang
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 26:4036-4041
Starting with a lead [1,5-a]pyrimidin-7(4H)-one-containing molecule (1), we generated potent, selective and orally bioavailable KDM5 inhibitors. Using structure- and property-based approaches, we designed 48 with improved cell potency (PC9 H3K4Me3 EC
Autor:
Robert M. Campbell, Yves Leblanc, James E. Audia, Jennifer A. Mertz, Brian K. Albrecht, Michael R. Cooper, Jeffrey G. Supko, Emmanuel Normant, Florence Poy, Christopher G. Nasveschuk, Richard T. Cummings, Michael C. Hewitt, Adrianne Neiss, Victor S. Gehling, Louise Bergeron, Jean-Christophe Harmange, Peter Sandy, Michael O'Meara, Alexander M. Taylor, Robert J. Sims, Nico Cantone, Eneida Pardo, Alexandre Côté, Shivangi Joshi, Hariharan Jayaram, Rishi G. Vaswani, Steve Bellon
Publikováno v:
Journal of Medicinal Chemistry. 59:1330-1339
In recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important di
Autor:
Jennifer A. Mertz, Michael C. Hewitt, Hari Jayaram, Yves Leblanc, Richard T. Cummings, Robert J. Sims, Eneida Pardo, Alexandre Côté, Alex M. Taylor, Christopher G. Nasveschuk, Jeremy W. Setser, Brian K. Albrecht, Steve Bellon, Jean-Christophe Harmange, James E. Audia, Jose M. Lora, Florence Poy, Shivangi Joshi, Rishi G. Vaswani, Yong Tang, Peter Sandy, Victor S. Gehling, Adrianne Neiss
Publikováno v:
ACS Medicinal Chemistry Letters. 7:145-150
Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report s
Autor:
Barbara M. Bryant, Patrick Trojer, Emmanuel Normant, Richard T. Cummings, Nico Cantone, Victor S. Gehling, William D. Bradley, Les A. Dakin, Rishi G. Vaswani, Chih-Chi Yuan, Kaylyn E. Williamson, Robert E. Campbell, Jean-Christophe Harmange, James E. Audia, Jacqui Méndez, Jennifer Busby, Christopher G. Nasveschuk, Feng Zhao, Danette L. Daniels, Brian K. Albrecht, Shivani Garapaty-Rao, Andrew S. Cook, Charlie Hatton, Srividya Balasubramanian, Shilpi Arora, Priyadarshini Iyer
Publikováno v:
Chemistry & Biology. 21(11):1463-1475
SummaryThe histone lysine methyltransferase (MT) Enhancer of Zeste Homolog 2 (EZH2) is considered an oncogenic driver in a subset of germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) and follicular lymphoma due to the presence of
Autor:
Victor S. Gehling, Richard T. Cummings, Yichin Liu, Patrick Trojer, Shilpi Arora, Shobu Odate, Yves Leblanc, Kaylyn E. Williamson, Fei Lan, James E. Audia, Erica VanderPorten, Brian K. Albrecht, Jean-Christophe Harmange, Weifeng Mao, Florence Poy, Louise Bergeron, Steven F. Bellon, Peter Sandy, Shane Buker, Amy Gustafson, Christopher M. Bailey
Publikováno v:
Bioorganicmedicinal chemistry letters. 26(17)
This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10 nM inhibitor of KDM5A. Compoun
Autor:
Erica L. Jackson, Shobu Odate, Robert M. Pitti, Gulfem D. Guler, David Arnott, Brian K. Albrecht, Jean-Christophe Harmange, Ganapati V. Hegde, Victor S. Gehling, Matthew Wongchenko, Shilpi Arora, Pranoti Gangurde, Wanda Manieri, Yibin Yang, Catherine Wilson, Patrick Trojer, Hyojin Kim, Jennifer Busby, Amy Gustafson, E. Megan Flynn, Christopher M. Bailey, Marie Classon, Yichin Liu, Tommy K. Cheung, Andrea G. Cochran, Tobias M. Maile, James R. Kiefer, Fei Lan, Charles Tindell, Kaylyn E. Williamson, Ted Lau, Steve Bellon, Maia Vinogradova, Richard T. Cummings, Michael R. Costa
Publikováno v:
Nature chemical biology. 12(7)
The KDM5 family of histone demethylases catalyzes the demethylation of histone H3 on lysine 4 (H3K4) and is required for the survival of drug-tolerant persister cancer cells (DTPs). Here we report the discovery and characterization of the specific KD