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259 results on '"McCabe, Michael T."'

3. GSK137, a potent small-molecule BCL6 inhibitor with in vivo activity, suppresses antibody responses in mice

Author

Pearce, Andrew C., Bamford, Mark J., Barber, Ruth, Bridges, Angela, Convery, Maire A., Demetriou, Constantinos, Evans, Sian, Gobbetti, Thomas, Hirst, David J., Holmes, Duncan S., Hutchinson, Jonathan P., Jayne, Sandrine, Lezina, Larissa, McCabe, Michael T., Messenger, Cassie, Morley, Joanne, Musso, Melissa C., Scott-Stevens, Paul, Manso, Ana Sousa, Schofield, Jennifer, Slocombe, Tom, Somers, Don, Walker, Ann L., Wyce, Anastasia, Zhang, Xi-Ping, and Wagner, Simon D.

Published
2021
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4. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia

Author

Pappalardi, Melissa B., Keenan, Kathryn, Cockerill, Mark, Kellner, Wendy A., Stowell, Alexandra, Sherk, Christian, Wong, Kristen, Pathuri, Sarath, Briand, Jacques, Steidel, Michael, Chapman, Philip, Groy, Arthur, Wiseman, Ashley K., McHugh, Charles F., Campobasso, Nino, Graves, Alan P., Fairweather, Emma, Werner, Thilo, Raoof, Ali, Butlin, Roger J., Rueda, Lourdes, Horton, John R., Fosbenner, David T., Zhang, Cunyu, Handler, Jessica L., Muliaditan, Morris, Mebrahtu, Makda, Jaworski, Jon-Paul, McNulty, Dean E., Burt, Charlotte, Eberl, H. Christian, Taylor, Amy N., Ho, Thau, Merrihew, Susan, Foley, Shawn W., Rutkowska, Anna, Li, Mei, Romeril, Stuart P., Goldberg, Kristin, Zhang, Xing, Kershaw, Christopher S., Bantscheff, Marcus, Jurewicz, Anthony J., Minthorn, Elisabeth, Grandi, Paola, Patel, Mehul, Benowitz, Andrew B., Mohammad, Helai P., Gilmartin, Aidan G., Prinjha, Rab K., Ogilvie, Donald, Carpenter, Christopher, Heerding, Dirk, Baylin, Stephen B., Jones, Peter A., Cheng, Xiaodong, King, Bryan W., Luengo, Juan I., Jordan, Allan M., Waddell, Ian, Kruger, Ryan G., and McCabe, Michael T.

Published
2021
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6. Dnmt1 has de novo activity targeted to transposable elements

Author

Haggerty, Chuck, Kretzmer, Helene, Riemenschneider, Christina, Kumar, Abhishek Sampath, Mattei, Alexandra L., Bailly, Nina, Gottfreund, Judith, Giesselmann, Pay, Weigert, Raha, Brändl, Björn, Giehr, Pascal, Buschow, René, Galonska, Christina, von Meyenn, Ferdinand, Pappalardi, Melissa B., McCabe, Michael T., Wittler, Lars, Giesecke-Thiel, Claudia, Mielke, Thorsten, Meierhofer, David, Timmermann, Bernd, Müller, Franz-Josef, Walter, Jörn, and Meissner, Alexander

Published
2021
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7. Reductive carboxylation supports redox homeostasis during anchorage-independent growth.

Author

Jiang, Lei, Shestov, Alexander A, Swain, Pamela, Yang, Chendong, Parker, Seth J, Wang, Qiong A, Terada, Lance S, Adams, Nicholas D, McCabe, Michael T, Pietrak, Beth, Schmidt, Stan, Metallo, Christian M, Dranka, Brian P, Schwartz, Benjamin, and DeBerardinis, Ralph J

Subjects
Cell Line, Tumor, Spheroids, Cellular, Extracellular Matrix, Mitochondria, Cytosol, Humans, Neoplasms, Reactive Oxygen Species, Citric Acid, Isocitrates, NADP, Isocitrate Dehydrogenase, Glucose, Glutamic Acid, Glutamine, Cell Adhesion, Cell Proliferation, Cell Hypoxia, Contact Inhibition, Oxidation-Reduction, Oxidative Stress, Homeostasis, General Science & Technology
Abstract

Cells receive growth and survival stimuli through their attachment to an extracellular matrix (ECM). Overcoming the addiction to ECM-induced signals is required for anchorage-independent growth, a property of most malignant cells. Detachment from ECM is associated with enhanced production of reactive oxygen species (ROS) owing to altered glucose metabolism. Here we identify an unconventional pathway that supports redox homeostasis and growth during adaptation to anchorage independence. We observed that detachment from monolayer culture and growth as anchorage-independent tumour spheroids was accompanied by changes in both glucose and glutamine metabolism. Specifically, oxidation of both nutrients was suppressed in spheroids, whereas reductive formation of citrate from glutamine was enhanced. Reductive glutamine metabolism was highly dependent on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor. This activity occurred in absence of hypoxia, a well-known inducer of reductive metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and suppressing IDH1 reduced spheroid growth through a mechanism requiring mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate produced reductively in the cytosol could enter the mitochondria and participate in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth. Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the mitochondrial citrate transporter protein. Together, the data indicate that adaptation to anchorage independence requires a fundamental change in citrate metabolism, initiated by IDH1-dependent reductive carboxylation and culminating in suppression of mitochondrial ROS.

Published
2016

8. Momelotinib: Mechanism of action, clinical, and translational science.

Author

Vlasakakis, Georgios, McCabe, Michael T., Ho, Yu Liu, Ferron‐Brady, Geraldine, Martin, Paul, Bentley, Darren, Ellis, Catherine, Antonysamy, Mary, and Visser, Sandra A. G.

Subjects
*MYELOPROLIFERATIVE neoplasms, *PROGNOSIS, *MYELOFIBROSIS, *SURVIVAL rate, *BONE marrow
Abstract

Myelofibrosis is a chronic myeloproliferative disorder characterized by bone marrow fibrosis, splenomegaly, anemia, and constitutional symptoms, with a median survival of ≈6 years from diagnosis. While currently approved Janus kinase (JAK) inhibitors (ruxolitinib, fedratinib) improve splenomegaly and symptoms, most can exacerbate myelofibrosis‐related anemia, a negative prognostic factor for survival. Momelotinib is a novel JAK1/JAK2/activin A receptor type 1 (ACVR1) inhibitor approved in the US, European Union, and the UK and is the first JAK inhibitor indicated specifically for patients with myelofibrosis with anemia. Momelotinib not only addresses the splenomegaly and symptoms associated with myelofibrosis by suppressing the hyperactive JAK–STAT (signal transducer and activator of transcription) pathway but also improves anemia and reduces transfusion dependency through ACVR1 inhibition. The recommended dose of momelotinib is 200 mg orally once daily, which was established after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Momelotinib is metabolized primarily by CYP3A4 and excreted as metabolites in feces and urine. Steady‐state maximum concentration is 479 ng/mL (CV%, 61%), with a mean AUCtau of 3288 ng.h/mL (CV%, 60%); its major metabolite, M21, is active (≈40% of pharmacological activity of parent), with a metabolite‐to‐parent AUC ratio of 1.4–2.1. This review describes momelotinib's mechanism of action, detailing how the JAK–STAT pathway is involved in myelofibrosis pathogenesis and ACVR1 inhibition decreases hepcidin, leading to improved erythropoiesis. Additionally, it summarizes the pivotal studies and data that informed the recommended dosage and risk/benefit assessment. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Supplemental Figure from A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Author

Dawson, Mark A., primary, Borthakur, Gautam, primary, Huntly, Brian J.P., primary, Karadimitris, Anastasios, primary, Alegre, Adrian, primary, Chaidos, Aristeidis, primary, Vogl, Dan T., primary, Pollyea, Daniel A., primary, Davies, Faith E., primary, Morgan, Gareth J., primary, Glass, Jacob L., primary, Kamdar, Manali, primary, Mateos, Maria-Victoria, primary, Tovar, Natalia, primary, Yeh, Paul, primary, Delgado, Regina García, primary, Basheer, Faisal, primary, Marando, Ludovica, primary, Gallipoli, Paolo, primary, Wyce, Anastasia, primary, Krishnatry, Anu Shilpa, primary, Barbash, Olena, primary, Bakirtzi, Evi, primary, Ferron-Brady, Geraldine, primary, Karpinich, Natalie O., primary, McCabe, Michael T., primary, Foley, Shawn W., primary, Horner, Thierry, primary, Dhar, Arindam, primary, Kremer, Brandon E., primary, and Dickinson, Michael, primary

Published
2023
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10. Supplementary Data1 from A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Author

Dawson, Mark A., primary, Borthakur, Gautam, primary, Huntly, Brian J.P., primary, Karadimitris, Anastasios, primary, Alegre, Adrian, primary, Chaidos, Aristeidis, primary, Vogl, Dan T., primary, Pollyea, Daniel A., primary, Davies, Faith E., primary, Morgan, Gareth J., primary, Glass, Jacob L., primary, Kamdar, Manali, primary, Mateos, Maria-Victoria, primary, Tovar, Natalia, primary, Yeh, Paul, primary, Delgado, Regina García, primary, Basheer, Faisal, primary, Marando, Ludovica, primary, Gallipoli, Paolo, primary, Wyce, Anastasia, primary, Krishnatry, Anu Shilpa, primary, Barbash, Olena, primary, Bakirtzi, Evi, primary, Ferron-Brady, Geraldine, primary, Karpinich, Natalie O., primary, McCabe, Michael T., primary, Foley, Shawn W., primary, Horner, Thierry, primary, Dhar, Arindam, primary, Kremer, Brandon E., primary, and Dickinson, Michael, primary

Published
2023
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11. Data from A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Author

Dawson, Mark A., primary, Borthakur, Gautam, primary, Huntly, Brian J.P., primary, Karadimitris, Anastasios, primary, Alegre, Adrian, primary, Chaidos, Aristeidis, primary, Vogl, Dan T., primary, Pollyea, Daniel A., primary, Davies, Faith E., primary, Morgan, Gareth J., primary, Glass, Jacob L., primary, Kamdar, Manali, primary, Mateos, Maria-Victoria, primary, Tovar, Natalia, primary, Yeh, Paul, primary, Delgado, Regina García, primary, Basheer, Faisal, primary, Marando, Ludovica, primary, Gallipoli, Paolo, primary, Wyce, Anastasia, primary, Krishnatry, Anu Shilpa, primary, Barbash, Olena, primary, Bakirtzi, Evi, primary, Ferron-Brady, Geraldine, primary, Karpinich, Natalie O., primary, McCabe, Michael T., primary, Foley, Shawn W., primary, Horner, Thierry, primary, Dhar, Arindam, primary, Kremer, Brandon E., primary, and Dickinson, Michael, primary

Published
2023
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12. Data from PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry

Author

Patel, Amish J., primary, Warda, Sarah, primary, Maag, Jesper L.V., primary, Misra, Rohan, primary, Miranda-Román, Miguel A., primary, Pachai, Mohini R., primary, Lee, Cindy J., primary, Li, Dan, primary, Wang, Naitao, primary, Bayshtok, Gabriella, primary, Fishinevich, Eve, primary, Meng, Yinuo, primary, Wong, Elissa W.P., primary, Yan, Juan, primary, Giff, Emily, primary, Pappalardi, Melissa B., primary, McCabe, Michael T., primary, Fletcher, Jonathan A., primary, Rudin, Charles M., primary, Chandarlapaty, Sarat, primary, Scandura, Joseph M., primary, Koche, Richard P., primary, Glass, Jacob L., primary, Antonescu, Cristina R., primary, Zheng, Deyou, primary, Chen, Yu, primary, and Chi, Ping, primary

Published
2023
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13. Supplementary Data from PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry

Author

Patel, Amish J., primary, Warda, Sarah, primary, Maag, Jesper L.V., primary, Misra, Rohan, primary, Miranda-Román, Miguel A., primary, Pachai, Mohini R., primary, Lee, Cindy J., primary, Li, Dan, primary, Wang, Naitao, primary, Bayshtok, Gabriella, primary, Fishinevich, Eve, primary, Meng, Yinuo, primary, Wong, Elissa W.P., primary, Yan, Juan, primary, Giff, Emily, primary, Pappalardi, Melissa B., primary, McCabe, Michael T., primary, Fletcher, Jonathan A., primary, Rudin, Charles M., primary, Chandarlapaty, Sarat, primary, Scandura, Joseph M., primary, Koche, Richard P., primary, Glass, Jacob L., primary, Antonescu, Cristina R., primary, Zheng, Deyou, primary, Chen, Yu, primary, and Chi, Ping, primary

Published
2023
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14. Supplementary Table 1 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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16. Supplementary Table 3 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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18. Supplementary Figure 3 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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19. Supplementary Figure 4 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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20. Data from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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21. Supplementary Figure 6 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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22. Supplementary Table 2 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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23. Supplementary Figure 2 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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24. Supplementary Figure 7 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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25. Supplementary Figure 5 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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26. Supplementary Figure 1 from A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation

Author

Ott, Heidi M., primary, Graves, Alan P., primary, Pappalardi, Melissa B., primary, Huddleston, Michael, primary, Halsey, Wendy S., primary, Hughes, Ashley M., primary, Groy, Arthur, primary, Dul, Edward, primary, Jiang, Yong, primary, Bai, Yuchen, primary, Annan, Roland, primary, Verma, Sharad K., primary, Knight, Steven D., primary, Kruger, Ryan G., primary, Dhanak, Dashyant, primary, Schwartz, Benjamin, primary, Tummino, Peter J., primary, Creasy, Caretha L., primary, and McCabe, Michael T., primary

Published
2023
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27. A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC

Author

Mohammad, Helai P., Smitheman, Kimberly N., Kamat, Chandrashekhar D., Soong, David, Federowicz, Kelly E., Van Aller, Glenn S., Schneck, Jess L., Carson, Jeffrey D., Liu, Yan, Butticello, Michael, Bonnette, William G., Gorman, Shelby A., Degenhardt, Yan, Bai, Yuchen, McCabe, Michael T., Pappalardi, Melissa B., Kasparec, Jiri, Tian, Xinrong, McNulty, Kenneth C., Rouse, Meagan, McDevitt, Patrick, Ho, Thau, Crouthamel, Michelle, Hart, Timothy K., Concha, Nestor O., McHugh, Charles F., Miller, William H., Dhanak, Dashyant, Tummino, Peter J., Carpenter, Christopher L., Johnson, Neil W., Hann, Christine L., and Kruger, Ryan G.

Published
2015
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28. Supplementary Data from Phase I Study of the Novel Enhancer of Zeste Homolog 2 (EZH2) Inhibitor GSK2816126 in Patients with Advanced Hematologic and Solid Tumors

Author

Yap, Timothy A., primary, Winter, Jane N., primary, Giulino-Roth, Lisa, primary, Longley, Jemma, primary, Lopez, Juanita, primary, Michot, Jean-Marie, primary, Leonard, John P., primary, Ribrag, Vincent, primary, McCabe, Michael T., primary, Creasy, Caretha L., primary, Stern, Melissa, primary, Pene Dumitrescu, Teodora, primary, Wang, Xiaowei, primary, Frey, Steve, primary, Carver, Jennifer, primary, Horner, Thierry, primary, Oh, Choon, primary, Khaled, Ahmed, primary, Dhar, Arindam, primary, and Johnson, Peter W.M., primary

Published
2023
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40. MEK inhibitors overcome resistance to BET inhibition across a number of solid and hematologic cancers

Author

Wyce, Anastasia, Matteo, Jeanne J., Foley, Shawn W., Felitsky, Daniel J., Rajapurkar, Satyajit R., Zhang, Xi-Ping, Musso, Melissa C., Korenchuk, Susan, Karpinich, Natalie O., Keenan, Kathryn M., Stern, Melissa, Mathew, Lijoy K., McHugh, Charles F., McCabe, Michael T., Tummino, Peter J., Kruger, Ryan G., Carpenter, Christopher, and Barbash, Olena

Published
2018
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41. A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies

Author

Dawson, Mark A., primary, Borthakur, Gautam, additional, Huntly, Brian J.P., additional, Karadimitris, Anastasios, additional, Alegre, Adrian, additional, Chaidos, Aristeidis, additional, Vogl, Dan T., additional, Pollyea, Daniel A., additional, Davies, Faith E., additional, Morgan, Gareth J., additional, Glass, Jacob L., additional, Kamdar, Manali, additional, Mateos, Maria-Victoria, additional, Tovar, Natalia, additional, Yeh, Paul, additional, Delgado, Regina García, additional, Basheer, Faisal, additional, Marando, Ludovica, additional, Gallipoli, Paolo, additional, Wyce, Anastasia, additional, Krishnatry, Anu Shilpa, additional, Barbash, Olena, additional, Bakirtzi, Evi, additional, Ferron-Brady, Geraldine, additional, Karpinich, Natalie O., additional, McCabe, Michael T., additional, Foley, Shawn W., additional, Horner, Thierry, additional, Dhar, Arindam, additional, Kremer, Brandon E., additional, and Dickinson, Michael, additional

Published
2022
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42. EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation

Author

Béguelin, Wendy, Popovic, Relja, Teater, Matt, Jiang, Yanwen, Bunting, Karen L., Rosen, Monica, Shen, Hao, Yang, Shao Ning, Wang, Ling, Ezponda, Teresa, Martinez-Garcia, Eva, Zhang, Haikuo, Zheng, Yupeng, Verma, Sharad K., McCabe, Michael T., Ott, Heidi M., Van Aller, Glenn S., Kruger, Ryan G., Liu, Yan, McHugh, Charles F., Scott, David W., Chung, Young Rock, Kelleher, Neil, Shaknovich, Rita, Creasy, Caretha L., Gascoyne, Randy D., Wong, Kwok-Kin, Cerchietti, Leandro, Levine, Ross L., Abdel-Wahab, Omar, Licht, Jonathan D., Elemento, Olivier, and Melnick, Ari M.

Published
2013
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43. Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2

Author

Ler, Lian Dee, Ghosh, Sujoy, Chai, Xiaoran, Thike, Aye Aye, Heng, Hong Lee, Siew, Ee Yan, Dey, Sucharita, Koh, Liang Kai, Lim, Jing Quan, Lim, Weng Khong, Myint, Swe Swe, Loh, Jia Liang, Ong, Pauline, Sam, Xin Xiu, Huang, Dachuan, Lim, Tony, Tan, Puay Hoon, Nagarajan, Sanjanaa, Cheng, Christopher Wai Sam, Ho, Henry, Ng, Lay Guat, Yuen, John, Lin, Po-Hung, Chuang, Cheng-Keng, Chang, Ying-Hsu, Weng, Wen-Hui, Rozen, Steven G., Tan, Patrick, Creasy, Caretha L., Pang, See-Tong, McCabe, Michael T., Poon, Song Ling, and Teh, Bin Tean

Published
2017
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45. Development and Validation of Reagents and Assays for EZH2 Peptide and Nucleosome High-Throughput Screens

Author

Diaz, Elsie, Machutta, Carl A., Chen, Stephanie, Jiang, Yong, Nixon, Christopher, Hofmann, Glenn, Key, Danielle, Sweitzer, Sharon, Patel, Mehul, Wu, Zining, Creasy, Caretha L., Kruger, Ryan G., LaFrance, Louis, Verma, Sharad K., Pappalardi, Melissa B., Le, Baochau, Van Aller, Glenn S., McCabe, Michael T., Tummino, Peter J., Pope, Andrew J., Thrall, Sara H., Schwartz, Benjamin, and Brandt, Martin

Published
2012
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46. List of Contributors

Author

Bantignies, Frédéric, primary, Bracken, Adrian P., additional, Cavalli, Giacomo, additional, Ciferri, Claudio, additional, Cochran, Andrea G., additional, Conway, Eric M., additional, Graves, Alan P., additional, Holoch, Daniel, additional, Huang, Christine S., additional, Kim, Chongwoo A., additional, Kruger, Ryan G., additional, Li, Li, additional, Liu, Nan, additional, Margueron, Raphaël, additional, McCabe, Michael T., additional, Min, Jinrong, additional, Nogales, Eva, additional, Pirrotta, Vincenzo, additional, Qin, Su, additional, Schwartz, Yuri B., additional, Tursun, Baris, additional, and Zhu, Bing, additional

Published
2017
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47. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)

Author

McCabe, Michael T., Graves, Alan P., Ganji, Gopinath, Diaz, Elsie, Halsey, Wendy S., Jiang, Yong, Smitheman, Kimberly N., Ott, Heidi M., Pappalardi, Melissa B., Allen, Kimberly E., Chen, Stephanie B., Pietra, Anthony Della, Dul, Edward, Hughes, Ashley M., Gilbert, Seth A., Thrall, Sara H., Tummino, Peter J., Kruger, Ryan G., Brandt, Martin, Schwartz, Benjamin, and Creasy, Caretha L.

Published
2012

48. PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry

Author

Patel, Amish J., primary, Warda, Sarah, additional, Maag, Jesper L.V., additional, Misra, Rohan, additional, Miranda-Román, Miguel A., additional, Pachai, Mohini R., additional, Lee, Cindy J., additional, Li, Dan, additional, Wang, Naitao, additional, Bayshtok, Gabriella, additional, Fishinevich, Eve, additional, Meng, Yinuo, additional, Wong, Elissa W.P., additional, Yan, Juan, additional, Giff, Emily, additional, Pappalardi, Melissa B., additional, McCabe, Michael T., additional, Fletcher, Jonathan A., additional, Rudin, Charles M., additional, Chandarlapaty, Sarat, additional, Scandura, Joseph M., additional, Koche, Richard P., additional, Glass, Jacob L., additional, Antonescu, Cristina R., additional, Zheng, Deyou, additional, Chen, Yu, additional, and Chi, Ping, additional

Published
2022
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49. In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor

Author

Gilmartin, Aidan G., Groy, Arthur, Gore, Elizabeth R., Atkins, Charity, Long, Edward R., Montoute, Monica N., Wu, Zining, Halsey, Wendy, McNulty, Dean E., Ennulat, Daniela, Rueda, Lourdes, Pappalardi, Melissa B., Kruger, Ryan G., McCabe, Michael T., Raoof, Ali, Butlin, Roger, Stowell, Alexandra, Cockerill, Mark, Waddell, Ian, Ogilvie, Donald, Luengo, Juan, Jordan, Allan, and Benowitz, Andrew B.

Subjects
hemic and lymphatic diseases, embryonic structures, Article
Abstract

Pharmacological induction of fetal hemoglobin (HbF) expression is an effective therapeutic strategy for the management of β-hemoglobinopathies such as sickle cell disease. DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-aza) and 5-aza-2′-deoxycytidine (decitabine) have been shown to induce HbF expression in both preclinical models and clinical studies, but are not currently approved for the management of hemoglobinopathies. We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364. This molecule potently inhibits the methyltransferase activity of DNMT1, but not DNMT family members DNMT3A or DNMT3B. In contrast with cytidine analog DNMT inhibitors, the DNMT1 inhibitory mechanism of GSK3482364 does not require DNA incorporation and is reversible. In cultured human erythroid progenitor cells, GSK3482364 decreased overall DNA methylation resulting in derepression of the -globin genes HBG1 and HBG2 and increased HbF expression. In a transgenic mouse model of sickle cell disease, orally administered GSK3482364 caused significant increases in both HbF levels and in the percentage HbF-expressing erythrocytes, with good overall tolerability. We conclude that in these preclinical models, selective, reversible inhibition of DNMT1 is sufficient for the induction of HbF, and is well-tolerated. We anticipate that GSK3482364 will be a useful tool molecule for the further study of selective DNMT1 inhibition both in vitro and in vivo.

Published
2020

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