Search Results - "Szewczuk, Lawrence"

Discovery of Potent and Orally Bioavailable Pyridine N‑Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions by Xu, Guozhang, Liu, Zhijie, Wang, Xinkang, Lu, Tianbao, DesJarlais, Renee L., Thieu, Tho, Zhang, Jing, Devine, Zheng Huang, Du, Fuyong, Li, Qiu, Milligan, Cynthia M., Shaffer, Paul, Cedervall, Peder E., Spurlino, John C., Stratton, Christopher F., Pietrak, Beth, Szewczuk, Lawrence M., Wong, Victoria, Steele, Ruth A., Bruinzeel, Wouter, Chintala, Madhu, Silva, Jose, Gaul, Michael D., Macielag, Mark J., Nargund, Ravi

“…Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent…”
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Structural Basis for the Inhibition of the LSD1 Histone Demethylase by the Antidepressant trans-2-Phenylcyclopropylamine by Yang, Maojun, Culhane, Jeffrey C, Szewczuk, Lawrence M, Jalili, Pegah, Ball, Haydn L, Machius, Mischa, Cole, Philip A, Yu, Hongtao

“…Histone modifications, such as acetylation and methylation, are important epigenetic marks that regulate diverse biological processes that use chromatin as the…”
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Structural basis of histone demethylation by LSD1 revealed by suicide inactivation by Szewczuk, Lawrence M, Tomchick, Diana R, Yang, Maojun, Machius, Mischa, Cole, Philip A, Gocke, Christian B, Yu, Hongtao, Brautigam, Chad A, Culhane, Jeffrey C

“…Histone methylation regulates diverse chromatin-templated processes, including transcription. The recent discovery of the first histone lysine-specific…”
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Development of a high-content imaging assay for screening compound aggregation by Jiang, Yong, Hoffman, Ann, Quinque, Geoffrey, Bonnette, William G., Szewczuk, Lawrence M., Holbert, Marc A., Gross, Jeffrey

“…Aggregated compounds can promiscuously and nonspecifically associate with proteins resulting in either false inhibition or activation of many different protein…”
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High-Throughput Assessment of Structural Continuity in Biologics by Musetti, Caterina, Bean, Mark F, Quinque, Geoffrey T, Kwiatkowski, Christopher, Szewczuk, Lawrence M, Baldoni, John, Zajac, Matthew A

“…We demonstrate a high-throughput chemoprinting platform that confirms the consistency in the higher-order structure of protein biologics and is sensitive…”
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Pharmacologic Characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a Reversible, Selective, and Potent Monoacylglycerol Lipase Inhibitor by Wyatt, Ryan M, Fraser, Ian, Welty, Natalie, Lord, Brian, Wennerholm, Michelle, Sutton, Steven, Ameriks, Michael K, Dugovic, Christine, Yun, Sujin, White, Allison, Nguyen, Leslie, Koudriakova, Tatiana, Tian, Gaochao, Suarez, Javier, Szewczuk, Lawrence, Bonnette, William, Ahn, Kay, Ghosh, Brahma, Flores, Christopher M, Connolly, Peter J, Zhu, Bin, Macielag, Mark J, Brandt, Michael R, Chevalier, Kristen, Zhang, Sui-Po, Lovenberg, Timothy, Bonaventure, Pascal

“…The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol…”
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Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents by Szewczuk, Lawrence M, Forti, Luca, Stivala, Lucia A, Penning, Trevor M

“…Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a phytoalexin found in grapes that has anti-inflammatory, cardiovascular protective, and cancer…”
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Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors by Lin, Hong, Zeng, Jin, Xie, Ren, Schulz, Mark J, Tedesco, Rosanna, Qu, Junya, Erhard, Karl F, Mack, James F, Raha, Kaushik, Rendina, Alan R, Szewczuk, Lawrence M, Kratz, Patricia M, Jurewicz, Anthony J, Cecconie, Ted, Martens, Stan, McDevitt, Patrick J, Martin, John D, Chen, Stephenie B, Jiang, Yong, Nickels, Leng, Schwartz, Benjamin J, Smallwood, Angela, Zhao, Baoguang, Campobasso, Nino, Qian, Yanqiu, Briand, Jacques, Rominger, Cynthia M, Oleykowski, Catherine, Hardwicke, Mary Ann, Luengo, Juan I

“…A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by…”
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A Mechanism-Based Inactivator for Histone Demethylase LSD1 by Culhane, Jeffrey C, Szewczuk, Lawrence M, Liu, Xin, Da, Guoping, Marmorstein, Ronen, Cole, Philip A

“…Histone demethylase LSD1 is a flavin-dependent amine oxidase that catalyzes the oxidative removal of one or two methyl groups from the methyl-lysine-4 side…”
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Modular Protein Ligation: A New Paradigm as a Reagent Platform for Pre-Clinical Drug Discovery by Matico, Rosalie, Szewczuk, Lawrence M., Pietrak, Beth, Chen, Stephanie, Dul, Ed, Bonnette, William G., Meinhold, Derrick W., Quinque, Geoffrey, Totoritis, Rachel, Lewis, Tia, Grimes, Maggie, Fornwald, Daniel, McCormick, Patricia M., Schaber, Michael, Jiang, Yong, Bledsoe, Randy, Holbert, Marc A.

“…Significant resource is spent by drug discovery project teams to generate numerous, yet unique target constructs for the multiple platforms used to drive drug…”
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Mechanistic Analysis of a Suicide Inactivator of Histone Demethylase LSD1 by Szewczuk, Lawrence M, Culhane, Jeffrey C, Yang, Maojun, Majumdar, Ananya, Yu, Hongtao, Cole, Philip A

“…Lysine-specific demethylase 1 (LSD1) is a transcriptional repressor and a flavin-dependent amine oxidase that is responsible for the removal of methyl from…”
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Development of nonsteroidal anti-inflammatory drug analogs and steroid carboxylates selective for human aldo-keto reductase isoforms: potential antineoplastic agents that work independently of cyclooxygenase isozymes by Bauman, David R, Rudnick, Stephen I, Szewczuk, Lawrence M, Jin, Yi, Gopishetty, Sridhar, Penning, Trevor M

“…Human aldo-keto reductases (AKRs) regulate nuclear receptors by controlling ligand availability. Enzymes implicated in regulating ligand occupancy and…”
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Protein phosphorylation by semisynthesis: from paper to practice by Szewczuk, Lawrence M, Tarrant, Mary Katherine, Cole, Philip A

“…Deconvolution of specific phosphorylation events can be complicated by the reversibility of modification. Protein semisynthesis with phosphonate analogues…”
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Formation of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones:  Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling by Park, Jong-Heum, Gopishetty, Sridhar, Szewczuk, Lawrence M, Troxel, Andrea B, Harvey, Ronald G, Penning, Trevor M

“…Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and procarcinogens that require activation by host metabolism. Metabolic…”
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Development of a high-throughput screen to detect inhibitors of TRPS1 sumoylation by Brandt, Martin, Szewczuk, Lawrence M, Zhang, Hong, Hong, Xuan, McCormick, Patricia M, Lewis, Tia S, Graham, Taylor I, Hung, Sunny T, Harper-Jones, Amber D, Kerrigan, John J, Wang, Da-Yuan, Dul, Edward, Hou, Wangfang, Ho, Thau F, Meek, Thomas D, Cheung, Mui H, Johanson, Kyung O, Jones, Christopher S, Schwartz, Benjamin, Kumar, Sanjay, Oliff, Allen I, Kirkpatrick, Robert B

“…Small ubiquitin-like modifier (SUMO) belongs to the family of ubiquitin-like proteins (Ubls) that can be reversibly conjugated to target-specific lysines on…”
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Analysis of Serotonin N-Acetyltransferase Regulation in Vitro and in Live Cells Using Protein Semisynthesis by Szewczuk, Lawrence M, Tarrant, Mary K, Sample, Vedangi, Drury, William J, Zhang, Jin, Cole, Philip A

“…Serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AANAT)] is a key circadian rhythm enzyme that drives the nocturnal production of melatonin…”
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De Novo Discovery of Serotonin N-Acetyltransferase Inhibitors by Szewczuk, Lawrence M, Saldanha, S. Adrian, Ganguly, Surajit, Bowers, Erin M, Javoroncov, Margarita, Karanam, Balasubramanyam, Culhane, Jeffrey C, Holbert, Marc A, Klein, David C, Abagyan, Ruben, Cole, Philip A

“…Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is a member of the GCN5 N-acetyltransferase (GNAT) superfamily and catalyzes the…”
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Mechanism-Based Inactivation of COX-1 by Red Wine m-Hydroquinones:  A Structure−Activity Relationship Study by Szewczuk, Lawrence M, Penning, Trevor M

“…Resveratrol (1) is a m-hydroquinone found in red wine, which has antiinflammatory, cardiovascular protective (antiplatelet), and cancer chemopreventive…”
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Viniferin Formation by COX-1:  Evidence for Radical Intermediates during Co-oxidation of Resveratrol by Szewczuk, Lawrence M, Lee, Seon Hwa, Blair, Ian A, Penning, Trevor M

“…Resveratrol (1) is a polyphenolic natural product, which functions as both a mechanism-based inactivator and a co-reductant of the COX-1 peroxidase. These…”
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Peptide Aldehyde Inhibitors of Cathepsin K Inhibit Bone Resorption Both In Vitro and In Vivo by Votta, Bartholomew J., Levy, Mark A., Badger, Alison, Bradbeer, Jeremy, Dodds, Robert A., James, Ian E., Thompson, Scott, Bossard, Mary J., Carr, Thomas, Connor, Janice R., Tomaszek, Thaddeus A., Szewczuk, Lawrence, Drake, Fred H., Veber, Daniel F., Gowen, Maxine

“…We have shown previously that cathepsin K, a recently identified member of the papain superfamily of cysteine proteases, is expressed selectively in…”
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