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Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development

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Oncology Research, Protein Dynamics DPU, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania 19426, United States
Screening and Compound Profiling, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania 19426, United States
§ Screening and Compound Profiling, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27713, United States
Biomolecular Structure, Computational and Structural Chemistry, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, United States
*(J.M.A.) Phone: 610-270-6368. E-mail: [email protected]
Cite this: ACS Med. Chem. Lett. 2013, 4, 10, 964–968
Publication Date (Web):August 12, 2013
Copyright © 2013 American Chemical Society

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    We recently reported the discovery of GSK2606414 (1), a selective first in class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), which inhibited PERK activation in cells and demonstrated tumor growth inhibition in a human tumor xenograft in mice. In continuation of our drug discovery program, we applied a strategy to decrease inhibitor lipophilicity as a means to improve physical properties and pharmacokinetics. This report describes our medicinal chemistry optimization culminating in the discovery of the PERK inhibitor GSK2656157 (6), which was selected for advancement to preclinical development.

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    General synthetic scheme and experimental procedures for the synthesis of compounds 212, DMPK, and biological assay descriptions, crystallographic methods, and kinase selectivity profile information. This material is available free of charge via the Internet at

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    9. Debasmita Mukherjee, Srija Chakraborty, Lena Bercz, Liliana D’Alesio, Jessica Wedig, Molly A. Torok, Timothy Pfau, Hannah Lathrop, Shrina Jasani, Abigail Guenther, Jake McGue, Daniel Adu-Ampratwum, James R. Fuchs, Timothy L. Frankel, Maciej Pietrzak, Stacey Culp, Anne M. Strohecker, Aleksander Skardal, Thomas A. Mace. Tomatidine targets ATF4-dependent signaling and induces ferroptosis to limit pancreatic cancer progression. iScience 2023, 26 (8) , 107408.
    10. Valerie Perea, Christian Cole, Justine Lebeau, Vivian Dolina, Kelsey R Baron, Aparajita Madhavan, Jeffery W Kelly, Danielle A Grotjahn, R Luke Wiseman. PERK signaling promotes mitochondrial elongation by remodeling membrane phosphatidic acid. The EMBO Journal 2023, 219
    11. Lilach Barer, Sarah K. Schröder, Ralf Weiskirchen, Eran Bacharach, Marcelo Ehrlich. Lipocalin-2 regulates the expression of interferon-stimulated genes and the susceptibility of prostate cancer cells to oncolytic virus infection. European Journal of Cell Biology 2023, 102 (2) , 151328.
    12. Wei Wang, Adam M. Hawkridge, Yibao Ma, Bei Zhang, John B. Mangrum, Zaneera H. Hassan, Tianhai He, Sofiya Blat, Chunqing Guo, Huiping Zhou, Jinze Liu, Xiang-Yang Wang, Xianjun Fang. Ubiquitin-like protein 5 is a novel player in the UPR-PERK arm and ER stress-induced cell death. Journal of Biological Chemistry 2023, 143 , 104915.
    13. Camilla Scarpellini, Sophie Valembois, Kenneth Goossens, Mike Vadi, Caroline Lanthier, Greta Klejborowska, Pieter Van Der Veken, Hans De Winter, Mathieu J. M. Bertrand, Koen Augustyns. From PERK to RIPK1: Design, synthesis and evaluation of novel potent and selective necroptosis inhibitors. Frontiers in Chemistry 2023, 11
    14. Juan Jin, Yuhao Xie, Jin-Shi Zhang, Jing-Quan Wang, Shi-Jie Dai, Wen-fang He, Shou-Ye Li, Charles R. Ashby, Zhe-Sheng Chen, Qiang He. Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers. Drug Resistance Updates 2023, 67 , 100929.
    15. Yalcin Erzurumlu, Hatice Kubra Dogan, Deniz Catakli. Progesterone regulates the endoplasmic reticulum-associated degradation and Unfolded Protein Response axis by mimicking the androgenic stimulation in prostate cancer cells. Molecular Biology Reports 2023, 50 (2) , 1253-1265.
    16. Jia Wen Yeap, Mei Lan Tan. Endoplasmic Reticulum Stress and Emerging Therapeutic Targets in Cancer. 2023, 1-54.
    17. Zhi-wei Ye, Jie Zhang, Muhammad Aslam, Anna Blumental-Perry, Kenneth D. Tew, Danyelle M. Townsend. Protein disulfide isomerase family mediated redox regulation in cancer. 2023, 83-106.
    18. Sujata Saraswat Ohri, Kariena Andres, Russell M. Howard, Brandon L. Brown, Michael D. Forston, Michal Hetman, Scott R. Whittemore. Acute pharmacological inhibition of PERK signaling after spinal cord injury spares oligodendrocytes and improves locomotor recovery. Journal of Neurotrauma 2022, 127
    19. Lucile Yart, Daniel Bastida-Ruiz, Mathilde Allard, Pierre-Yves Dietrich, Patrick Petignat, Marie Cohen. Linking unfolded protein response to ovarian cancer cell fusion. BMC Cancer 2022, 22 (1)
    20. Di Xu, Zhen Liu, Ming-Xing Liang, Yin-Jiao Fei, Wei Zhang, Yang Wu, Jin-Hai Tang. Endoplasmic reticulum stress targeted therapy for breast cancer. Cell Communication and Signaling 2022, 20 (1)
    21. Wioleta Dudka, Grazyna Hoser, Shamba S. Mondal, Laura Turos-Korgul, Julian Swatler, Monika Kusio-Kobialka, Magdalena Wołczyk, Agata Klejman, Marta Brewinska-Olchowik, Agata Kominek, Milena Wiech, Marcin M. Machnicki, Ilona Seferynska, Tomasz Stoklosa, Katarzyna Piwocka. Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS/RAF/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells. BMC Cancer 2022, 22 (1)
    22. Nasim Ebrahimi, Jamileh Saremi, Masoud Ghanaatian, Elnaz Yazdani, Samaneh Adelian, Sahar Samsami, Neda Moradi, Nadi Rostami Ravari, Amirhossein Ahmadi, Michael R. Hamblin, Amir Reza Aref. The role of endoplasmic reticulum stress in the regulation of long noncoding RNAs in cancer. Journal of Cellular Physiology 2022, 237 (10) , 3752-3767.
    23. Liliana M. Almeida, Brígida R. Pinho, Michael R. Duchen, Jorge M. A. Oliveira. The PERKs of mitochondria protection during stress: insights for PERK modulation in neurodegenerative and metabolic diseases. Biological Reviews 2022, 97 (5) , 1737-1748.
    24. Sauyeun Shin, Jacobo Solorzano, Mehdi Liauzun, Stéphane Pyronnet, Corinne Bousquet, Yvan Martineau. Translational alterations in pancreatic cancer: a central role for the integrated stress response. NAR Cancer 2022, 4 (4)
    25. Zhiyuan Fang, Wenwen Gao, Qianming Jiang, Juan J. Loor, Chenchen Zhao, Xiliang Du, Min Zhang, Yuxiang Song, Zhe Wang, Guowen Liu, Xinwei Li, Lin Lei. Targeting IRE1α and PERK in the endoplasmic reticulum stress pathway attenuates fatty acid-induced insulin resistance in bovine hepatocytes. Journal of Dairy Science 2022, 105 (8) , 6895-6908.
    26. Bernard Gallez. The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia. Frontiers in Pharmacology 2022, 13
    27. Avital Schwed-Gross, Hila Hamiel, Gabriel P. Faber, Mor Angel, Rakefet Ben-Yishay, Jennifer I. C. Benichou, Dana Ishay-Ronen, Yaron Shav-Tal. Glucocorticoids enhance chemotherapy-driven stress granule assembly and impair granule dynamics, leading to cell death. Journal of Cell Science 2022, 135 (14)
    28. Linluo Zhang, Jie Zhou, Zhe Feng, Baoping Jiang, Changqing Li, Lingling Zhou, Xueping Zhou. Qingluo Tongbi Formula Alleviates Hepatotoxicity Induced by Tripterygium wilfordii Hook. F. by Regulating Excessive Mitophagy Through the PERK-ATF4 Pathway. Frontiers in Pharmacology 2022, 13
    29. Heather A. Walters, Brenda H. Welter, Harrison C. Moss, Martha A. Villano, Ronny Orobio-Hurtado, William J. Sullivan, Lesly A. Temesvari, . Eukaryotic Initiation Factor 2α Kinases Regulate Virulence Functions, Stage Conversion, and the Stress Response in Entamoeba invadens. mSphere 2022, 7 (3)
    30. Lisa G. M. Huis in ’t Veld, Nataschja I. Ho, Melisssa Wassink, Martijn H. den Brok, Gosse J. Adema. Saponin-based adjuvant-induced dendritic cell cross-presentation is dependent on PERK activation. Cellular and Molecular Life Sciences 2022, 79 (5)
    31. Smit Kour, Sandeep Rana, Sydney P. Kubica, Smitha Kizhake, Mudassier Ahmad, Catalina Muñoz-Trujillo, David Klinkebiel, Sarbjit Singh, Jayapal Reddy Mallareddy, Surabhi Chandra, Nicholas T. Woods, Adam R. Karpf, Amarnath Natarajan. Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells. Journal of Biological Chemistry 2022, 298 (5) , 101890.
    32. Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Soo Han Bae. PERK prevents hepatic lipotoxicity by activating the p62-ULK1 axis-mediated noncanonical KEAP1-Nrf2 pathway. Redox Biology 2022, 50 , 102235.
    33. Nanhui Jiang, Rong Huang, Jiahao Zhang, Dongxue Xu, Tianlong Li, Zhongyi Sun, Lianjiu Su, Zhiyong Peng. TIMP2 mediates endoplasmic reticulum stress contributing to sepsis‐induced acute kidney injury. The FASEB Journal 2022, 36 (4)
    34. Scott M Ebert, Blake B Rasmussen, Andrew R Judge, Sarah M Judge, Lars Larsson, Ronald C Wek, Tracy G Anthony, George R Marcotte, Matthew J Miller, Mark A Yorek, Adrian Vella, Elena Volpi, Jennifer I Stern, Matthew D Strub, Zachary Ryan, John J Talley, Christopher M Adams. Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy. The Journal of Nutrition 2022, 152 (4) , 926-938.
    35. Han Gao, Chengwei He, Rongxuan Hua, Yuexin Guo, Boya Wang, Chen Liang, Lei Gao, Hongwei Shang, Jing-Dong Xu. Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases. Frontiers in Molecular Biosciences 2022, 9
    36. Eugenia Licari, Luis Sánchez-del-Campo, Paola Falletta. The two faces of the Integrated Stress Response in cancer progression and therapeutic strategies. The International Journal of Biochemistry & Cell Biology 2021, 139 , 106059.
    37. Dong Liang, Mohammad Khoonkari, Tony Avril, Eric Chevet, Frank A.E. Kruyt. The unfolded protein response as regulator of cancer stemness and differentiation: Mechanisms and implications for cancer therapy. Biochemical Pharmacology 2021, 192 , 114737.
    38. Aparna Anand, Abhinay Sharma, Miriam Ravins, Debabrata Biswas, Poornima Ambalavanan, Kimberly Xuan Zhen Lim, Rachel Ying Min Tan, Atul Kumar Johri, Boaz Tirosh, Emanuel Hanski. Unfolded protein response inhibitors cure group A streptococcal necrotizing fasciitis by modulating host asparagine. Science Translational Medicine 2021, 13 (605)
    39. Hsiao-Sang Chu, Cornelia Peterson, Albert Jun, James Foster. Targeting the integrated stress response in ophthalmology. Current Eye Research 2021, 46 (8) , 1075-1088.
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    41. Yingying Shi, Yichao Lu, Jian You. Unfolded protein response in the activation-induced biological processes of CD8+ T cells. Pharmacological Research 2021, 169 , 105654.
    42. Mohammed Mufrrih, Biyao Chen, Shiu-Wan Chan, . Zika Virus Induces an Atypical Tripartite Unfolded Protein Response with Sustained Sensor and Transient Effector Activation and a Blunted BiP Response. mSphere 2021, 6 (3)
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    45. Andreia Mendes, Julien P Gigan, Christian Rodriguez Rodrigues, Sébastien A Choteau, Doriane Sanseau, Daniela Barros, Catarina Almeida, Voahirana Camosseto, Lionel Chasson, Adrienne W Paton, James C Paton, Rafael J Argüello, Ana-Maria Lennon-Duménil, Evelina Gatti, Philippe Pierre. Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4. Life Science Alliance 2021, 4 (2) , e202000865.
    46. Amit Kumar, Anu Rahal, Jagdip Singh Sohal, Vivek Kumar Gupta. Bacterial stress response: understanding the molecular mechanics to identify possible therapeutic targets. Expert Review of Anti-infective Therapy 2021, 19 (2) , 121-127.
    47. Mari McMahon, Afshin Samali, Eric Chevet. Maintenance of Endoplasmic Reticulum Protein Homeostasis in Cancer: Friend or Foe. 2021, 197-214.
    48. Rashedul Alam, Mohammad Mamun Ur Rashid, Mohammad Fazlul Kabir, Hyung-Ryong Kim. Endoplasmic reticulum stress and organoids. Organoid 2021, 1 , e3.
    49. Alina Küper, Jennifer Baumann, Kirsten Göpelt, Melanie Baumann, Christopher Sänger, Eric Metzen, Philip Kranz, Ulf Brockmeier. Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis. Cell Death & Disease 2021, 12 (1)
    50. Shujing Liu, Weilin Wang, Yu Liu, Wanqing Cao, Pei Yuan, Jiaxin Li, Xiaorui Song, Lingling Wang, Linsheng Song. Protein kinase-like ER kinase (PERK) regulates autophagy of hemocytes in antiviral immunity of Pacific oyster Crassostrea gigas. Fish and Shellfish Immunology Reports 2020, 1 , 100002.
    51. Tianming Zhao, Juan Du, Hui Zeng. Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer. Journal of Hematology & Oncology 2020, 13 (1)
    52. Rachel E. Sexton, Mohammed Najeeb Al Hallak, Maria Diab, Asfar S. Azmi. Gastric cancer: a comprehensive review of current and future treatment strategies. Cancer and Metastasis Reviews 2020, 39 (4) , 1179-1203.
    53. Jeffrey J. Rodvold, Su Xian, Julia Nussbacher, Brian Tsui, T. Cameron Waller, Stephen C. Searles, Alyssa Lew, Pengfei Jiang, Ivan Babic, Natsuko Nomura, Jonathan H. Lin, Santosh Kesari, Hannah Carter, Maurizio Zanetti. IRE1α and IGF signaling predict resistance to an endoplasmic reticulum stress-inducing drug in glioblastoma cells. Scientific Reports 2020, 10 (1)
    54. Philip Kranz, Christopher Sänger, Alexandra Wolf, Jennifer Baumann, Eric Metzen, Melanie Baumann, Kirsten Göpelt, Ulf Brockmeier. Tumor cells rely on the thiol oxidoreductase PDI for PERK signaling in order to survive ER stress. Scientific Reports 2020, 10 (1)
    55. Anna Constance Vind, Aitana Victoria Genzor, Simon Bekker-Jensen. Ribosomal stress-surveillance: three pathways is a magic number. Nucleic Acids Research 2020, 48 (19) , 10648-10661.
    56. Ali Khateb, Ze’ev A. Ronai. Unfolded Protein Response in Leukemia: From Basic Understanding to Therapeutic Opportunities. Trends in Cancer 2020, 6 (11) , 960-973.
    57. Julia M.D. Grandjean, R.Luke Wiseman. Small molecule strategies to harness the unfolded protein response: where do we go from here?. Journal of Biological Chemistry 2020, 295 (46) , 15692-15711.
    58. Giulia Emanuelli, Nikou Nassehzadeh-Tabriz, Nick W. Morrell, Stefan J. Marciniak. The integrated stress response in pulmonary disease. European Respiratory Review 2020, 29 (157) , 200184.
    59. Glowi Alasiri, Yannasittha Jiramongkol, Sasanan Trakansuebkul, Hui-Ling Ke, Zimam Mahmud, Kitti Intuyod, Eric W.-F. Lam. Reciprocal regulation between GCN2 (eIF2AK4) and PERK (eIF2AK3) through the JNK-FOXO3 axis to modulate cancer drug resistance and clonal survival. Molecular and Cellular Endocrinology 2020, 515 , 110932.
    60. Claudio Hetz, Kezhong Zhang, Randal J. Kaufman. Mechanisms, regulation and functions of the unfolded protein response. Nature Reviews Molecular Cell Biology 2020, 21 (8) , 421-438.
    61. Rebecca M. Sebastian, Matthew D. Shoulders. Chemical Biology Framework to Illuminate Proteostasis. Annual Review of Biochemistry 2020, 89 (1) , 529-555.
    62. Alyssa Batista, Jeffrey J. Rodvold, Su Xian, Stephen C. Searles, Alyssa Lew, Takao Iwawaki, Gonzalo Almanza, T. Cameron Waller, Jonathan Lin, Kristen Jepsen, Hannah Carter, Maurizio Zanetti, . IRE1α regulates macrophage polarization, PD-L1 expression, and tumor survival. PLOS Biology 2020, 18 (6) , e3000687.
    63. Eran Mick, Denis V Titov, Owen S Skinner, Rohit Sharma, Alexis A Jourdain, Vamsi K Mootha. Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell. eLife 2020, 9
    64. Hendrik Luesch, Ville O. Paavilainen. Natural products as modulators of eukaryotic protein secretion. Natural Product Reports 2020, 37 (5) , 717-736.
    65. Tingting Zhang, Ningning Li, Chaoyang Sun, Yang Jin, Xia Sheng. MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?. EMBO Molecular Medicine 2020, 12 (5)
    66. Stefanie Schmidt, Sarah Denk, Armin Wiegering. Targeting Protein Synthesis in Colorectal Cancer. Cancers 2020, 12 (5) , 1298.
    67. Aastha Kapoor, Carolyn G. Chen, Renato V. Iozzo. Endorepellin evokes an angiostatic stress signaling cascade in endothelial cells. Journal of Biological Chemistry 2020, 295 (19) , 6344-6356.
    68. Anqi Li, No-Joon Song, Brian P. Riesenberg, Zihai Li. The Emerging Roles of Endoplasmic Reticulum Stress in Balancing Immunity and Tolerance in Health and Diseases: Mechanisms and Opportunities. Frontiers in Immunology 2020, 10
    69. Sarah Bond, Claudia Lopez-Lloreda, Patrick J Gannon, Cagla Akay-Espinoza, Kelly L Jordan-Sciutto. The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration. Journal of Neuropathology & Experimental Neurology 2020, 79 (2) , 123-143.
    70. Cynthia Lebeaupin, Jing Yong, Randal J. Kaufman. The Impact of the ER Unfolded Protein Response on Cancer Initiation and Progression: Therapeutic Implications. 2020, 113-131.
    71. Yangjie Liao, Bo Duan, Yufei Zhang, Xinmin Zhang, Bin Xia. Excessive ER-phagy mediated by the autophagy receptor FAM134B results in ER stress, the unfolded protein response, and cell death in HeLa cells. Journal of Biological Chemistry 2019, 294 (52) , 20009-20023.
    72. Sifan Chen, Ayana Henderson, Michael C. Petriello, Kymberleigh A. Romano, Mary Gearing, Ji Miao, Mareike Schell, Walter J. Sandoval-Espinola, Jiahui Tao, Bingdong Sha, Mark Graham, Rosanne Crooke, Andre Kleinridders, Emily P. Balskus, Federico E. Rey, Andrew J. Morris, Sudha B. Biddinger. Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction. Cell Metabolism 2019, 30 (6) , 1141-1151.e5.
    73. Isabelle C. Romine, R. Luke Wiseman. PERK Signaling Regulates Extracellular Proteostasis of an Amyloidogenic Protein During Endoplasmic Reticulum Stress. Scientific Reports 2019, 9 (1)
    74. Zhi Zheng, Yuxi Shang, Jiahui Tao, Jun Zhang, Bingdong Sha. Endoplasmic Reticulum Stress Signaling Pathways: Activation and Diseases. Current Protein & Peptide Science 2019, 20 (9) , 935-943.
    75. Sakiko Nishikawa, Yuka Itoh, Muneshige Tokugawa, Yasumichi Inoue, Ken-ichi Nakashima, Yuka Hori, Chiharu Miyajima, Kou Yoshida, Daisuke Morishita, Nobumichi Ohoka, Makoto Inoue, Hajime Mizukami, Toshiaki Makino, Hidetoshi Hayashi. Kurarinone from Sophora Flavescens Roots Triggers ATF4 Activation and Cytostatic Effects Through PERK Phosphorylation. Molecules 2019, 24 (17) , 3110.
    76. Rie Hantani, Saya Hanawa, Shohei Oie, Kayo Umetani, Toshihiro Sato, Yoshiji Hantani. Identification of a New Inhibitor That Stabilizes Interleukin-2-Inducible T-Cell Kinase in Its Inactive Conformation. SLAS Discovery 2019, 24 (8) , 854-862.
    77. Archana Kumari, Rajesh K. Singh. Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorganic Chemistry 2019, 89 , 103021.
    78. Claudio Hetz, Jeffrey M. Axten, John B. Patterson. Pharmacological targeting of the unfolded protein response for disease intervention. Nature Chemical Biology 2019, 15 (8) , 764-775.
    79. Wioletta Rozpędek, Dariusz Pytel, Alicja Nowak-Zduńczyk, Dawid Lewko, Radosław Wojtczak, J. Alan Diehl, Ireneusz Majsterek. Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment. Current Medicinal Chemistry 2019, 26 (8) , 1425-1445.
    80. Tianshu Liu, Alan W. Shindel, Guiting Lin, Tom F. Lue. Cellular signaling pathways modulated by low-intensity extracorporeal shock wave therapy. International Journal of Impotence Research 2019, 31 (3) , 170-176.
    81. Sheng-Kai Hsu, Chien-Chih Chiu, Hans-Uwe Dahms, Chon-Kit Chou, Chih-Mei Cheng, Wen-Tsan Chang, Kai-Chun Cheng, Hui-Min David Wang, I-Ling Lin. Unfolded Protein Response (UPR) in Survival, Dormancy, Immunosuppression, Metastasis, and Treatments of Cancer Cells. International Journal of Molecular Sciences 2019, 20 (10) , 2518.
    82. Diogo Trigo, André Nadais, Odete A.B. da Cruz e Silva. Unravelling protein aggregation as an ageing related process or a neuropathological response. Ageing Research Reviews 2019, 51 , 67-77.
    83. Alfonso Serrano-del Valle, Alberto Anel, Javier Naval, Isabel Marzo. Immunogenic Cell Death and Immunotherapy of Multiple Myeloma. Frontiers in Cell and Developmental Biology 2019, 7
    84. Lydia P. Liew, Dean C. Singleton, Way W. Wong, Gary J. Cheng, Stephen M. F. Jamieson, Michael P. Hay. Hypoxia‐Activated Prodrugs of PERK Inhibitors. Chemistry – An Asian Journal 2019, 14 (8) , 1238-1248.
    85. Devin Tauber, Roy Parker. 15-Deoxy-Δ12,14-prostaglandin J2 promotes phosphorylation of eukaryotic initiation factor 2α and activates the integrated stress response. Journal of Biological Chemistry 2019, 294 (16) , 6344-6352.
    86. Umut I. Onat, Asli D. Yildirim, Özlem Tufanli, Ismail Çimen, Begüm Kocatürk, Zehra Veli, Syed M. Hamid, Kenichi Shimada, Shuang Chen, Jon Sin, Prediman K. Shah, Roberta A. Gottlieb, Moshe Arditi, Ebru Erbay. Intercepting the Lipid-Induced Integrated Stress Response Reduces Atherosclerosis. Journal of the American College of Cardiology 2019, 73 (10) , 1149-1169.
    87. Yann S. Gallot, Kyle R. Bohnert, Alex R. Straughn, Guangyan Xiong, Sajedah M. Hindi, Ashok Kumar. PERK regulates skeletal muscle mass and contractile function in adult mice. The FASEB Journal 2019, 33 (2) , 1946-1962.
    88. Dean C. Singleton, Adrian L. Harris. ATF4, Hypoxia and Treatment Resistance in Cancer. 2019, 75-108.
    89. Vivek Kumar Pandey, Alpana Mathur, Poonam Kakkar. Emerging role of Unfolded Protein Response (UPR) mediated proteotoxic apoptosis in diabetes. Life Sciences 2019, 216 , 246-258.
    90. Aitor Almanza, Antonio Carlesso, Chetan Chintha, Stuart Creedican, Dimitrios Doultsinos, Brian Leuzzi, Andreia Luís, Nicole McCarthy, Luigi Montibeller, Sanket More, Alexandra Papaioannou, Franziska Püschel, Maria Livia Sassano, Josip Skoko, Patrizia Agostinis, Jackie de Belleroche, Leif A. Eriksson, Simone Fulda, Adrienne M. Gorman, Sandra Healy, Andrey Kozlov, Cristina Muñoz-Pinedo, Markus Rehm, Eric Chevet, Afshin Samali. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. The FEBS Journal 2019, 286 (2) , 241-278.
    91. Wen-Xiang Cao, Ting Li, Zheng-Hai Tang, Le-Le Zhang, Zhao-Yu Wang, Xia Guo, Min-Xia Su, Xiuping Chen, Jin-Jian Lu. MLKL mediates apoptosis via a mutual regulation with PERK/eIF2α pathway in response to reactive oxygen species generation. Apoptosis 2018, 23 (9-10) , 521-531.
    92. Cynthia Lebeaupin, Deborah Vallée, Younis Hazari, Claudio Hetz, Eric Chevet, Béatrice Bailly-Maitre. Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. Journal of Hepatology 2018, 69 (4) , 927-947.
    93. Pierre-Alain Thiebaut, Eugénie Delile, David Coquerel, Jean-Michel Brunel, Sylvanie Renet, Fabienne Tamion, Vincent Richard. Protein tyrosine phosphatase 1B regulates endothelial endoplasmic reticulum stress; role in endothelial dysfunction. Vascular Pharmacology 2018, 109 , 36-44.
    94. Eoghan McGrath, Susan Logue, Katarzyna Mnich, Shane Deegan, Richard Jäger, Adrienne Gorman, Afshin Samali. The Unfolded Protein Response in Breast Cancer. Cancers 2018, 10 (10) , 344.
    95. Hanley N. Abramson. The Multiple Myeloma Drug Pipeline—2018: A Review of Small Molecules and Their Therapeutic Targets. Clinical Lymphoma Myeloma and Leukemia 2018, 18 (9) , 611-627.
    96. Mayur Madhavan, Zachary S. Nevin, H. Elizabeth Shick, Eric Garrison, Cheryl Clarkson-Paredes, Molly Karl, Benjamin L. L. Clayton, Daniel C. Factor, Kevin C. Allan, Lilianne Barbar, Tanya Jain, Panagiotis Douvaras, Valentina Fossati, Robert H. Miller, Paul J. Tesar. Induction of myelinating oligodendrocytes in human cortical spheroids. Nature Methods 2018, 15 (9) , 700-706.
    97. Abbey D Zuehlke, Leonard Neckers. Cancer: Therapeutic Approaches Targeting Stress Pathways. 2018, 1-5.
    98. Kumari Asha, Neelam Sharma-Walia. Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics. Oncotarget 2018, 9 (61) , 31920-31936.
    99. Wing Y. Lam, Arijita Jash, Cong-Hui Yao, Lucas D’Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya. Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function. Cell Reports 2018, 24 (9) , 2479-2492.e6.
    100. Emiliya V. Nosova, Galina N. Lipunova, Valery N. Charushin, Oleg N. Chupakhin. Fluorine-containing indoles: Synthesis and biological activity. Journal of Fluorine Chemistry 2018, 212 , 51-106.
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