Data from Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib

Autor: Philip Jones, Nancy E. Kohl, Timothy P. Heffernan, Joseph R. Marszalek, Giulio F. Draetta, Andy M. Zuniga, Simon S. Yu, Christopher C. Williams, Erika Suzuki, Nakia D. Spencer, Sahil Seth, Vandhana Ramamoorthy, Michael Peoples, Robert A. Mullinax, Meredith A. Miller, Timothy McAfoos, Pijus K. Mandal, Xiaoyan Ma, Anastasia M. Lopez, Chiu-Yi Liu, Jeffrey J. Kovacs, Zhijun Kang, Yongying Jiang, Justin K. Huang, Virginia Giuliani, Sonal Gera, Guang Gao, Ningping Feng, Qing Chang, Christopher L. Carroll, Caroline C. Carrillo, Jason P. Burke, Christopher A. Bristow, Benjamin J. Bivona, Maria Emilia Di Francesco, Jason B. Cross, Connor A. Parker, Sarah Johnson, Qi Wu, Angela L. Harris, Faika Mseeh, Paul Leonard, Barbara Czako, Brooke A. Meyers, Yuting Sun

Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway. SHP2 inhibition has demonstrated tumor growth

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::679aa5c2787960118aa25b0d20d0a771
https://doi.org/10.1158/0008-5472.c.6512119.v1

Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme

Autor: Norma Rogers, Stephan Krapp, Faika Mseeh, Richard T. Lewis, Keith Mikule, Michelle Han, Jay Theroff, Yongying Jiang, Keith M. Wilcoxen, Cross Jason, Dana Pfaffinger, Michael J. Soth, Paul G. Leonard, Philip Jones, Pijus K. Mandal, Angela L. Harris, Martin R. Tremblay, Simon S. Yu, Jason P Burke, Connor A. Parker, Barbara Czako, Alessia Petrocchi, Naphtali J. Reyna, Joseph R. Marszalek, Matthew M. Hamilton, Timothy McAfoos, Brett W. Virgin-Downey, Graham Trevitt, Alfred Lammens, Alan Xu

Publikováno v: Journal of Medicinal Chemistry. 64:11302-11329

Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in the metabolism of l-tryptophan to kynurenine, has been widely explored as a potential immunotherapeutic target in oncology. We developed a class of

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec33cf6551a670d4d40eaab2894a6f60
https://doi.org/10.1021/acs.jmedchem.1c00679

Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response

Autor: Christine N. Spencer, Jennifer L. McQuade, Vancheswaran Gopalakrishnan, John A. McCulloch, Marie Vetizou, Alexandria P. Cogdill, Md A. Wadud Khan, Xiaotao Zhang, Michael G. White, Christine B. Peterson, Matthew C. Wong, Golnaz Morad, Theresa Rodgers, Jonathan H. Badger, Beth A. Helmink, Miles C. Andrews, Richard R. Rodrigues, Andrey Morgun, Young S. Kim, Jason Roszik, Kristi L. Hoffman, Jiali Zheng, Yifan Zhou, Yusra B. Medik, Laura M. Kahn, Sarah Johnson, Courtney W. Hudgens, Khalida Wani, Pierre-Olivier Gaudreau, Angela L. Harris, Mohamed A. Jamal, Erez N. Baruch, Eva Perez-Guijarro, Chi-Ping Day, Glenn Merlino, Barbara Pazdrak, Brooke S. Lochmann, Robert A. Szczepaniak-Sloane, Reetakshi Arora, Jaime Anderson, Chrystia M. Zobniw, Eliza Posada, Elizabeth Sirmans, Julie Simon, Lauren E. Haydu, Elizabeth M. Burton, Linghua Wang, Minghao Dang, Karen Clise-Dwyer, Sarah Schneider, Thomas Chapman, Nana-Ama A. S. Anang, Sheila Duncan, Joseph Toker, Jared C. Malke, Isabella C. Glitza, Rodabe N. Amaria, Hussein A. Tawbi, Adi Diab, Michael K. Wong, Sapna P. Patel, Scott E. Woodman, Michael A. Davies, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee, Patrick Hwu, Vanessa Jensen, Yardena Samuels, Ravid Straussman, Nadim J. Ajami, Kelly C. Nelson, Luigi Nezi, Joseph F. Petrosino, P. Andrew Futreal, Alexander J. Lazar, Jianhua Hu, Robert R. Jenq, Michael T. Tetzlaff, Yan Yan, Wendy S. Garrett, Curtis Huttenhower, Padmanee Sharma, Stephanie S. Watowich, James P. Allison, Lorenzo Cohen, Giorgio Trinchieri, Carrie R. Daniel, Jennifer A. Wargo

Publikováno v: Science (New York, N.Y.). 374(6575)

Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our un

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::333675406957cdc475454320562634b6
https://pubmed.ncbi.nlm.nih.gov/35235771

Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer

Autor: Akira Inoue, Takashi Shingu, Johnathon L. Rose, Xiaoyan Ma, Christopher A. Bristow, Takahiro Kodama, Alessandro Carugo, Andy M. Zuniga, Angela K. Deem, Giannicola Genovese, Timothy P. Heffernan, Bahar Salimian Rizi, Frederick S. Robinson, Joseph R. Daniele, Ningping Feng, Scott Kopetz, Rosalba Minelli, Mary Sobieski, Kadir C. Akdemir, Jason Roszik, Robert A. Mullinax, Sahil Seth, Michael Peoples, Hideo Tomihara, David G. Menter, Clifford Stephan, Sanjana Srinivasan, Giulio Draetta, Sara Loponte, Yonathan Lissanu Deribe, David Brunell, Virginia Giuliani, Tin Oo Khor, Angela L. Harris, Andrea Viale

Publikováno v: Gastroenterology. 161(1)

Background & Aims Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer. Methods To identify promising and clinicall

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f698b264050723f59e7b5f4cf101237
https://pubmed.ncbi.nlm.nih.gov/33798528

Abstract 2338: The GLS1 inhibitor IPN60090 enhances antitumor immune response through metabolic reprogramming of T cells and impacts on the tumor microenvironment

Autor: Timothy P. Heffernan, Michael J. Soth, Mikhila Mahendra, Nakia D. Spencer, Timothy A. Yap, Sonal Gera, Jennifer R. Molina, Erika Suzuki, Angela L. Harris, Jeffrey J. Kovacs, Giulio Draetta, Ningping Feng, Kang Le, Christopher A. Bristow, Philip Jones

Publikováno v: Cancer Research. 81:2338-2338

Therapeutic agents targeting metabolism in the tumor microenvironment have been of increasing interest in recent years, however, the complexities of the interplay between tumor, stromal and immune cell interactions add complexity to these therapeutic

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::5b9a5fe12ba1c0846d4f527998dd251b
https://doi.org/10.1158/1538-7445.am2021-2338