Search Results - "Wigle, Tim J."

Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2 by Knutson, Sarah K., Warholic, Natalie M., Wigle, Tim J., Klaus, Christine R., Allain, Christina J., Raimondi, Alejandra, Scott, Margaret Porter, Chesworth, Richard, Moyer, Mikel P., Copeland, Robert A., Richon, Victoria M., Pollock, Roy M., Kuntz, Kevin W., Keilhack, Heike

“…Inactivation of the switch/sucrose nonfermentable complex component SMARCB1 is extremely prevalent in pediatrie malignant rhabdoid tumors (MRTs) or atypical…”
Get full text

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma by Knutson, Sarah K, Kawano, Satoshi, Minoshima, Yukinori, Warholic, Natalie M, Huang, Kuan-Chun, Xiao, Yonghong, Kadowaki, Tadashi, Uesugi, Mai, Kuznetsov, Galina, Kumar, Namita, Wigle, Tim J, Klaus, Christine R, Allain, Christina J, Raimondi, Alejandra, Waters, Nigel J, Smith, Jesse J, Porter-Scott, Margaret, Chesworth, Richard, Moyer, Mikel P, Copeland, Robert A, Richon, Victoria M, Uenaka, Toshimitsu, Pollock, Roy M, Kuntz, Kevin W, Yokoi, Akira, Keilhack, Heike

“…Mutations within the catalytic domain of the histone methyltransferase EZH2 have been identified in subsets of patients with non-Hodgkin lymphoma (NHL). These…”
Get full text

A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells by Vedadi, Masoud, Barsyte-Lovejoy, Dalia, Liu, Feng, Rival-Gervier, Sylvie, Allali-Hassani, Abdellah, Labrie, Viviane, Wigle, Tim J, DiMaggio, Peter A, Wasney, Gregory A, Siarheyeva, Alena, Dong, Aiping, Tempel, Wolfram, Wang, Sun-Chong, Chen, Xin, Chau, Irene, Mangano, Thomas J, Huang, Xi-ping, Simpson, Catherine D, Pattenden, Samantha G, Norris, Jacqueline L, Kireev, Dmitri B, Tripathy, Ashutosh, Edwards, Aled, Roth, Bryan L, Janzen, William P, Garcia, Benjamin A, Petronis, Arturas, Ellis, James, Brown, Peter J, Frye, Stephen V, Arrowsmith, Cheryl H, Jin, Jian

“…Protein lysine methyltransferases modulate the activities of chromatin and non-chromatin proteins by specific methylation of lysine side chains. A large-scale…”
Get full text

A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells by Knutson, Sarah K, Wigle, Tim J, Warholic, Natalie M, Sneeringer, Christopher J, Allain, Christina J, Klaus, Christine R, Sacks, Joelle D, Raimondi, Alejandra, Majer, Christina R, Song, Jeffrey, Scott, Margaret Porter, Jin, Lei, Smith, Jesse J, Olhava, Edward J, Chesworth, Richard, Moyer, Mikel P, Richon, Victoria M, Copeland, Robert A, Keilhack, Heike, Pollock, Roy M, Kuntz, Kevin W

“…EZH2 is a protein methyltransferase component of the polycomb repressive complex 2 (PRC2) that installs the H3K27me3 chromatin mark. EPZ005687 inhibits EZH2…”
Get full text

The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat by Kuntz, Kevin W, Campbell, John E, Keilhack, Heike, Pollock, Roy M, Knutson, Sarah K, Porter-Scott, Margaret, Richon, Victoria M, Sneeringer, Chris J, Wigle, Tim J, Allain, Christina J, Majer, Christina R, Moyer, Mikel P, Copeland, Robert A, Chesworth, Richard

“…Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation…”
Get full text

A687V EZH2 is a gain-of-function mutation found in lymphoma patients by Majer, Christina R., Jin, Lei, Scott, Margaret Porter, Knutson, Sarah K., Kuntz, Kevin W., Keilhack, Heike, Smith, Jesse J., Moyer, Mikel P., Richon, Victoria M., Copeland, Robert A., Wigle, Tim J.

“…► Heterozygous EZH2 A687V mutation is associated with lymphoma. ► A687V EZH2 mutant shown to be active with altered substrate specificity. ► Mutation changes…”
Get full text

Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas by Knutson, Sarah K, Warholic, Natalie M, Johnston, L Danielle, Klaus, Christine R, Wigle, Tim J, Iwanowicz, Dorothy, Littlefield, Bruce A, Porter-Scott, Margaret, Smith, Jesse J, Moyer, Mikel P, Copeland, Robert A, Pollock, Roy M, Kuntz, Kevin W, Raimondi, Alejandra, Keilhack, Heike

“…Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and…”
Get full text

Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines by Liu, Feng, Chen, Xin, Allali-Hassani, Abdellah, Quinn, Amy M, Wigle, Tim J, Wasney, Gregory A, Dong, Aiping, Senisterra, Guillermo, Chau, Irene, Siarheyeva, Alena, Norris, Jacqueline L, Kireev, Dmitri B, Jadhav, Ajit, Herold, J. Martin, Janzen, William P, Arrowsmith, Cheryl H, Frye, Stephen V, Brown, Peter J, Simeonov, Anton, Vedadi, Masoud, Jin, Jian

“…Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human…”
Get full text

The Y641C mutation of EZH2 alters substrate specificity for histone H3 lysine 27 methylation states by Wigle, Tim J., Knutson, Sarah K., Jin, Lei, Kuntz, Kevin W., Pollock, Roy M., Richon, Victoria M., Copeland, Robert A., Scott, Margaret Porter

“…► Heterozygous EZH2 Y641C mutation is associated with lymphoma and myelodisplasia. ► Y641C EZH2 mutant shown to be active with altered substrate specificity. ►…”
Get full text

Identification of a peptide inhibitor for the histone methyltransferase WHSC1 by Morrison, Michael J, Boriack-Sjodin, P Ann, Swinger, Kerren K, Wigle, Tim J, Sadalge, Dipti, Kuntz, Kevin W, Scott, Margaret Porter, Janzen, William P, Chesworth, Richard, Duncan, Kenneth W, Harvey, Darren M, Lampe, John W, Mitchell, Lorna H, Copeland, Robert A

“…WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a…”
Get full text

Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds by Kireev, Dmitri, Wigle, Tim J, Norris-Drouin, Jacqueline, Herold, J. Martin, Janzen, William P, Frye, Stephen V

“…The malignant brain tumor (MBT) repeat is an important epigenetic-code “reader” and is functionally associated with differentiation, gene silencing, and tumor…”
Get full text

Inhibitors of RecA activity discovered by high-throughput screening: cell-permeable small molecules attenuate the SOS response in Escherichia coli by Wigle, Tim J, Sexton, Jonathan Z, Gromova, Anna V, Hadimani, Mallinath B, Hughes, Mark A, Smith, Ginger R, Yeh, Li-An, Singleton, Scott F

“…The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with nonclassical cellular targets. Unfortunately,…”
Get more information

A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models by Chan-Penebre, Elayne, Kuplast, Kristy G, Majer, Christina R, Boriack-Sjodin, P Ann, Wigle, Tim J, Johnston, L Danielle, Rioux, Nathalie, Munchhof, Michael J, Jin, Lei, Jacques, Suzanne L, West, Kip A, Lingaraj, Trupti, Stickland, Kimberly, Ribich, Scott A, Raimondi, Alejandra, Scott, Margaret Porter, Waters, Nigel J, Pollock, Roy M, Smith, Jesse J, Barbash, Olena, Pappalardi, Melissa, Ho, Thau F, Nurse, Kelvin, Oza, Khyati P, Gallagher, Kathleen T, Kruger, Ryan, Moyer, Mikel P, Copeland, Robert A, Chesworth, Richard, Duncan, Kenneth W

“…Protein methyltransferase PRMT5 symmetrically dimethylates arginine residues in proteins, including histones, and has been associated with tumorigenesis. The…”
Get full text

A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants by Schenkel, Laurie B, Molina, Jennifer R, Swinger, Kerren K, Abo, Ryan, Blackwell, Danielle J, Lu, Alvin Z, Cheung, Anne E, Church, W David, Kunii, Kaiko, Kuplast-Barr, Kristy G, Majer, Christina R, Minissale, Elena, Mo, Jan-Rung, Niepel, Mario, Reik, Christopher, Ren, Yue, Vasbinder, Melissa M, Wigle, Tim J, Richon, Victoria M, Keilhack, Heike, Kuntz, Kevin W

“…PARP14 has been implicated by genetic knockout studies to promote protumor macrophage polarization and suppress the antitumor inflammatory response due to its…”
Get more information

Drugging the human methylome: an emerging modality for reversible control of aberrant gene transcription by Wigle, Tim J, Copeland, Robert A

“…•Methylation of lysine, arginine and cytosine is important for epigenetic signaling.•An overview of the writers, erasers and readers of the methylome is…”
Get full text

Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound by Mitchell, Lorna H., Drew, Allison E., Ribich, Scott A., Rioux, Nathalie, Swinger, Kerren K., Jacques, Suzanne L., Lingaraj, Trupti, Boriack-Sjodin, P. Ann, Waters, Nigel J., Wigle, Tim J., Moradei, Oscar, Jin, Lei, Riera, Tom, Porter-Scott, Margaret, Moyer, Mikel P., Smith, Jesse J., Chesworth, Richard, Copeland, Robert A.

“…A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent,…”
Get full text

Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule by Wigle, Tim J., Ren, Yue, Molina, Jennifer R., Blackwell, Danielle J., Schenkel, Laurie B., Swinger, Kerren K., Kuplast‐Barr, Kristy, Majer, Christina R., Church, W. David, Lu, Alvin Z., Mo, Jason, Abo, Ryan, Cheung, Anne, Dorsey, Bryan W., Niepel, Mario, Perl, Nicholas R., Vasbinder, Melissa M., Keilhack, Heike, Kuntz, Kevin W.

“…PARP14 is an interferon‐stimulated gene that is overexpressed in multiple tumor types, influencing pro‐tumor macrophage polarization as well as suppressing the…”
Get full text

Small-Molecule Ligands of Methyl-Lysine Binding Proteins by Herold, J. Martin, Wigle, Tim J, Norris, Jacqueline L, Lam, Robert, Korboukh, Victoria K, Gao, Cen, Ingerman, Lindsey A, Kireev, Dmitri B, Senisterra, Guillermo, Vedadi, Masoud, Tripathy, Ashutosh, Brown, Peter J, Arrowsmith, Cheryl H, Jin, Jian, Janzen, William P, Frye, Stephen V

“…Proteins which bind methylated lysines (“readers” of the histone code) are important components in the epigenetic regulation of gene expression and can also…”
Get full text

Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L by Basavapathruni, Aravind, Jin, Lei, Daigle, Scott R., Majer, Christina R. A., Therkelsen, Carly A., Wigle, Tim J., Kuntz, Kevin W., Chesworth, Richard, Pollock, Roy M., Scott, Margaret P., Moyer, Mikel P., Richon, Victoria M., Copeland, Robert A., Olhava, Edward J.

“…DOT1L is the human protein methyltransferase responsible for catalyzing the methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L,…”
Get full text

EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity by Campbell, John E, Kuntz, Kevin W, Knutson, Sarah K, Warholic, Natalie M, Keilhack, Heike, Wigle, Tim J, Raimondi, Alejandra, Klaus, Christine R, Rioux, Nathalie, Yokoi, Akira, Kawano, Satoshi, Minoshima, Yukinori, Choi, Hyeong-Wook, Porter Scott, Margaret, Waters, Nigel J, Smith, Jesse J, Chesworth, Richard, Moyer, Mikel P, Copeland, Robert A

“…Inhibitors of the protein methyltransferase Enhancer of Zeste Homolog 2 (EZH2) may have significant therapeutic potential for the treatment of B cell lymphomas…”
Get full text