Zobrazeno 1 - 10
of 25
pro vyhledávání: '"John Lesnick"'
Miniaturization of High-Throughput Epigenetic Methyltransferase Assays with Acoustic Liquid Handling
Publikováno v:
SLAS Technology. 21:208-216
Epigenetics continues to emerge as an important target class for drug discovery and cancer research. As programs scale to evaluate many new targets related to epigenetic expression, new tools and techniques are required to enable efficient and reprod
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df53d7565643d1ca33f94301afa54b3d
https://doi.org/10.1177/2211068215610861
https://doi.org/10.1177/2211068215610861
Autor:
Jim Nonomiya, Laurent Salphati, Martin Augistin, Philip Stephen Jackson, Mario Mörtl, Steven Do, Steve Price, Robert Heald, Chudi Ndubaku, Binqing Wei, Timothy P. Heffron, Aleksander Kolesnikov, John Lesnick, Alan G. Olivero, Leslie Lee, Charles Eigenbrot, Graham Jones, Vickie Tsui, Wei Wei Prior, Neville James Mclean, Kyle A. Edgar, Emanuela Gancia, Deepak Sampath, Jodie Pang, Steven T. Staben, Stefan Steinbacher, Cristina Lewis, Jeffrey Wallin, Steve Sideris, Lori Friedman
Publikováno v:
Journal of Medicinal Chemistry. 59:985-1002
Inhibitors of the class I phosphoinositide 3-kinase (PI3K) isoform PI3Kα have received substantial attention for their potential use in cancer therapy. Despite the particular attraction of targeting PI3Kα, achieving selectivity for the inhibition o
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_________::b1f08fde479eb477dc008315bc97ce6a
https://doi.org/10.1021/acs.jmedchem.5b01483
https://doi.org/10.1021/acs.jmedchem.5b01483
Autor:
Laurent Salphati, Nicole Blaquiere, Cristina Lewis, Steven Do, Binqing Wei, Steven T. Staben, Aleksandr Kolesnikov, Alan G. Olivero, Erin K. Bradley, Jim Nonomiya, Lionel Rouge, Jenna Dotson, Jodie Pang, Vickie Tsui, John Lesnick, Richard Goldsmith, Timothy P. Heffron, Ping Wu, Jeremy Murray, Christian Wiesmann
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 23:897-901
Substructural class effects surrounding replacement of a 'cis' N-methyl aniline amide within potent and selective thienobenzoxepin PI3-kinase inhibitors are disclosed. While a simple aryl to alkyl switch was not tolerated due to differences in prefer
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63e276c9ba5f322f7d0b934889b837f9
https://doi.org/10.1016/j.bmcl.2012.10.121
https://doi.org/10.1016/j.bmcl.2012.10.121
Autor:
Jeffrey Wallin, Jodie Pang, Laurent Salphati, Stephen E. Gould, Leslie Lee, Jonathan Cheong, Cristina Lewis, Timothy P. Heffron, Xiaolin Zhang, Steve Sideris, Chudi Ndubaku, Jim Nonomiya, Joy Drobnick, Emile Plise, Lan Wang, Bruno Alicke, Alan G. Olivero, Kyle A. Edgar, John Lesnick
Publikováno v:
ACS medicinal chemistry letters. 7(4)
Inhibition of phosphoinositide 3-kinase (PI3K) signaling is an appealing approach to treat brain tumors, especially glioblastoma multiforme (GBM). We previously disclosed our successful approach to prospectively design potent and blood–brain barrie
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce007b2150b77e3550424574be811f9d
https://pubmed.ncbi.nlm.nih.gov/27096040
https://pubmed.ncbi.nlm.nih.gov/27096040
Autor:
Laurent Salphati, Stewart J. Baker, Steve Price, Jim Nonomiya, Matthew C. Lucas, Timothy Hancox, David Knowles, Bohdan Waszkowycz, Neil Anthony Pegg, David Chantry, Bryan K. Chan, Paul Blaney, Anthony Brown, Steven T. Staben, Jodie Pang, Paul Depledge, Rama K. Kondru, Mark Ultsch, Paul Goldsmith, Karin Reif, Angelina Bisconte, Cristina Lewis, Eileen Mary Seward, Jeremy Murray, Brian Safina, Daniel P. Sutherlin, Zachary Kevin Sweeney, Georgette Castanedo, David Michael Goldstein, Jasmit Kaur, Sukhjit Sohal, Binqing Wei, John Lesnick, Stephen J. Shuttleworth, Alan Nadin
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:4296-4302
A potent inhibitor of PI3Kδ that is ⩾200 fold selective for the remaining three Class I PI3K isoforms and additional kinases is described. The hypothesis for selectivity is illustrated through structure activity relationships and crystal structure
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::92be9aea35b7ac14f79d9d789ee6948b
https://doi.org/10.1016/j.bmcl.2012.05.027
https://doi.org/10.1016/j.bmcl.2012.05.027
Autor:
Marcia Belvin, Laurent Salphati, Leslie Lee, Daniel P. Sutherlin, Jodie Pang, Lori Friedman, Carol O'Brien, Jeffrey Wallin, Jane Guan, Jill M. Spoerke, Cristina Lewis, Robert Kassees, Wei Wei Prior, Olivero Alan G, Deepak Sampath, Leanne Ross, John Lesnick, Mark R. Lackner, Kyle A. Edgar, Sonal Patel, Megan Berry, Letitia Lensun, Jim Nonomiya
Publikováno v:
Molecular Cancer Therapeutics. 10:2426-2436
Alterations of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway occur broadly in cancer via multiple mechanisms including mutation of the PIK3CA gene, loss or mutation of phosphatase and tensin homolog (PTEN), and deregulation of mammalian
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::203d40e98934516668700c66434c1b8f
https://doi.org/10.1158/1535-7163.mct-11-0446
https://doi.org/10.1158/1535-7163.mct-11-0446
Autor:
Bing-Yan Zhu, Daniel J. Burdick, Cristina Lewis, Leslie Lee, Jodie Pang, Timothy P. Heffron, Lionel Rouge, Hoa Le, Jim Nonomiya, Michael Siu, Deepak Sampath, Christian Wiesmann, Alan G. Olivero, Laurent Salphati, Steven Do, Daniel P. Sutherlin, Ping Wu, Steve Sideris, Jeremy Murray, Steven T. Staben, Vickie Tsui, Richard Goldsmith, Wei Wei Prior, Jenna Dotson, John Lesnick
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 21:4054-4058
Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xe
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f3ae4dfd1334a411e6cc97f4dfb59ea
https://doi.org/10.1016/j.bmcl.2011.04.124
https://doi.org/10.1016/j.bmcl.2011.04.124
Autor:
Lori Friedman, Lionel Rouge, Daniel P. Sutherlin, Georgette Castanedo, Adrian Folkes, Nan Chi Wan, Wei Wei Prior, Shumei Wang, Emile Plise, Ping Wu, Seema R. Bhat, Cristina Lewis, Deepak Sampath, Jeremy Murray, Alan G. Olivero, Jim Nonomiya, Timothy P. Heffron, Leslie Lee, Laurent Salphati, Irina Chuckowree, Steven T. Staben, Vickie Tsui, Bing-Yan Zhu, Christian Weismann, Jenna Dotson, Jodie Pang, John Lesnick
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 20:6048-6051
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f5dfb15d68c0d5ace550e093eca7d77
https://doi.org/10.1016/j.bmcl.2010.08.067
https://doi.org/10.1016/j.bmcl.2010.08.067
Autor:
Cristina Lewis, Nan Chi Wan, Jennafer Dotson, Janet L. Gunzner, Georgette Castanedo, Deepak Sampath, Laurent Salphati, Jim Nonomiya, John Lesnick, Susan Wong, Timothy P. Heffron, Christine Chang, Megan Berry, Shumei Wang, Simon Mathieu, Jodie Pang, Steve Sideris, Adrian Folkes, Vickie Tsui, Irina Chuckowree, Daniel P. Sutherlin, Alan G. Olivero, David A. Peterson, Bing-Yan Zhu
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 20:2408-2411
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modi
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07054715432864ef6433675ccce8e7b4
https://doi.org/10.1016/j.bmcl.2010.03.046
https://doi.org/10.1016/j.bmcl.2010.03.046
Autor:
Shumei Wang, Susan Wong, Laurent Salphati, Simon Mathieu, John Lesnick, Deepak Sampath, Nan Chi Wan, Jodie Pang, Irina Chuckowree, Alan G. Olivero, Cristina Lewis, Daniel P. Sutherlin, Jim Nonomiya, Adrian Folkes, Zhigang Chang, Christian Wiesmann, Tim Heffron, Lori Friedman, Jenna Dotson, Richard Goldsmith, Georgette Castanedo, Wei Wei Prior, Steve Sideris, Leslie Lee, Vickie Tsui, Qingping Tian, Bing-Yan Zhu, Megan Berry
Publikováno v:
Journal of Medicinal Chemistry. 53:1086-1097
The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer. Starting with compounds 1 and 2 (GDC-0941) as templates, (thienopyrimidin-2-yl)aminopyrimidines were discovered as potent inhibitors of PI3K or both PI3K and mTOR. Structur
Externí odkaz:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a01dbe4957dc3c1f294e6e22c73dcc85
https://doi.org/10.1021/jm901284w
https://doi.org/10.1021/jm901284w