Article
Genetics & Heredity
Meareg Gebreegziabher Amare, Nathaniel M. Westrick, Nancy P. Keller, Mehdi Kabbage
Summary: Programmed cell death (PCD) is a crucially regulated process for the survival and development of all cellular life, extensively studied in animals but less understood in fungi. Inhibitors of apoptosis proteins (IAPs), broadly conserved in the fungal kingdom, play a role in fungal development and virulence, although their mechanisms and functions remain unclear.
FUNGAL GENETICS AND BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Federica Cossu, Simone Camelliti, Daniele Lecis, Luca Sorrentino, Maria Teresa Majorini, Mario Milani, Eloise Mastrangelo
Summary: Inhibitors of apoptosis proteins (IAPs) are important targets in cancer research, and the compound FC2 has been identified as a potential lead compound for the development of new IAP-antagonists for cancer treatment. FC2 can disrupt pro-survival pathways in cancer cells and induce cancer cell death, showing promise for combination therapy with other agents.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Immunology
Katherine S. Ventre, Kevin Roehle, Elisa Bello, Aladdin M. Bhuiyan, Tamara Biary, Stephanie J. Crowley, Patrick T. Bruck, Max Heckler, Patrick J. Lenehan, Lestat R. Ali, Courtney T. Stump, Victoria Lippert, Eleanor Clancy-Thompson, Winiffer D. Conce Alberto, Megan T. Hoffman, Li Qiang, Marc Pelletier, James J. Akin, Michael Dougan, Stephanie K. Dougan
Summary: Checkpoint blockade immunotherapy has failed in pancreatic cancer and other poorly responsive tumor types due to inadequate T cell priming. cIAP1/2 antagonists have pleiotropic beneficial effects on antitumor immunity, including increased activation and control of tumor growth, synergy with multiple immunotherapy modalities, and immunologic memory. This study confirms the importance of T cell-dependent antitumor immunity and provides insights into how rare T cells coordinate downstream immune responses.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Hideharu Hashimoto, Daniel H. Ramirez, Ophelie Lautier, Natalie Pawlak, Gunter Blobel, Benoit Palancade, Erik W. Debler
Summary: The study reports the retention of unspliced pre-mRNA by ScPml39 protein in Saccharomyces cerevisiae prior to export through nuclear pore complexes. The crystal structure of ScPml39 was determined, revealing its structural orthologs and providing insights into its function and mechanism.
SCIENTIFIC REPORTS
(2022)
Article
Biophysics
Hui Qi Ng, Qingxin Li, Congbao Kang
Summary: In this study, we reported NMR resonance assignments of the first BIR domain of human cIAP, and the dynamics of this domain were obtained. Our hydrogen-deuterium exchange experiment revealed the solvent exposure of the first helix in BIR1. The assigned backbone and side chain resonances will be useful for probing protein-protein interactions.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Biochemistry & Molecular Biology
Takuya Murata, Genta Ito, Naoko Utsunomiya-Tate
Summary: Tau, a microtubule-binding protein, is a major component of neurofibrillary tangles in Alzheimer's disease. D-isomerized Asp accumulation in Tau affects fibril morphology and weakens the potency of Tau aggregation inhibitors. This study provides insights into the impact of D-isomerization on Tau and its implications in Alzheimer's disease pathogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biology
Giuseppe Bombaci, Mayuresh Anant Sarangdhar, Nicola Andina, Aubry Tardivel, Eric Chi-Wang Yu, Gillian M. Mackie, Matthew Pugh, Vedat Burak Ozan, Yara Banz, Thibaud Spinetti, Cedric Hirzel, Esther Youd, Joerg Schefold, Graham Taylor, Amiq Gazdhar, Nicolas Bonadies, Anne Angelillo-Scherrer, Pascal Schneider, Kendle M. Maslowski, Ramanjaneyulu Allam
Summary: The protein RNH1 has been found to inhibit the activation of inflammasomes, reducing inflammation. Deletion of RNH1 in macrophages leads to increased production of IL-1β and activation of caspase-1. Furthermore, RNH1 protein levels were negatively correlated with disease severity and inflammation in COVID-19 patients.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Michele Fiore, Michele Mosconi, Francesco Boni, Alice Parodi, Annalisa Salis, Bruno Tasso, Eloise Mastrangelo, Enrico Millo, Federica Cossu
Summary: Inhibitor of Apoptosis Proteins (IAPs) are important targets for cancer therapy, but their activity regulation within the NF-kappa B pathway can cause chemoresistance. The molecule FC2 was found to modulate the NF-kappa B pathway in MDA-MB-231 adenocarcinoma cancer cells. FC2 combined with Smac-mimetics or TNF showed improved cytotoxic effects. The study also proposed 22 derivatives of FC2 with modified structures and evaluated their efficacy/potency in cells and binding affinity to the target proteins.
Article
Chemistry, Medicinal
Atsunori Kaneshige, Longchuan Bai, Mi Wang, Donna McEachern, Jennifer L. Meagher, Renqi Xu, Paul D. Kirchhoff, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: We discovered a potent and selective STAT5 degrader with strong antitumor activity in vivo. Using PROTAC technology, we transformed small-molecule ligands into selective STAT5 degraders, with AK-2292 as the best compound. AK-2292 effectively induced degradation of STAT5 proteins in AML cell lines and showed strong antitumor activity in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lauren B. Arendse, Gyles E. Cozier, Charles J. Eyermann, Gregory S. Basarab, Sylva L. Schwager, Kelly Chibale, K. Ravi Acharya, Edward D. Sturrock
Summary: This study investigates the structural requirements for potent dual cACE/NEP inhibition by synthesizing and analyzing the crystal structures of inhibitors with high resolution. The results highlight the importance of the interplay between the S-1' and S-2' subsites for the selectivity of ACE domain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Joanna M. Rhodes, Anthony R. Mato
Summary: Understanding the B cell receptor pathway and the development of targeted BCR inhibitors, such as ibrutinib, has transformed the treatment of CLL. However, many patients discontinue treatment due to adverse events. Zanubrutinib, a second-generation BTK inhibitor, shows promising efficacy and tolerability in early phase clinical trials.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Femi Olawale, Opeyemi Iwaloye, Olusola Olalekan Elekofehinti
Summary: The over-expression of PLK1 is linked to cancer prognosis, and this study identified potential inhibitors by targeting the NCD and PBD domains of PLK1 through pharmacophore modeling and molecular docking. The hit compounds showed promising inhibitory activity and drug-like properties for further experimental validation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Cell Biology
Celia X. -J. Chen, Wei Zhang, Shulan Qu, Fucan Xia, Yidong Zhu, Bo Chen
Summary: In this study, a novel small molecule inhibitor (QL-1200186) targeting the pseudokinase regulatory domain of TYK2 was developed, showing high affinity and potency in inhibiting TYK2. The inhibitor demonstrated no cross-reactivity with other JAK homologous kinase domains and exhibited promising pharmacokinetic profiles in mice. QL-1200186 could be a potential therapeutic candidate for psoriasis and other autoimmune diseases.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Multidisciplinary Sciences
Angela M. Crist, Kelly M. Hinkle, Xue Wang, Christina M. Moloney, Billie J. Matchett, Sydney A. Labuzan, Isabelle Frankenhauser, Nkem O. Azu, Amanda M. Liesinger, Elizabeth R. Lesser, Daniel J. Serie, Zachary S. Quicksall, Tulsi A. Patel, Troy P. Carnwath, Michael DeTure, Xiaojia Tang, Ronald C. Petersen, Ranjan Duara, Neill R. Graff-Radford, Mariet Allen, Minerva M. Carrasquillo, Hu Li, Owen A. Ross, Nilufer Ertekin-Taner, Dennis W. Dickson, Yan W. Asmann, Rickey E. Carter, Melissa E. Murray
Summary: Selective vulnerability of different brain regions is observed in many neurodegenerative disorders, with the hippocampus and cortex being particularly affected in Alzheimer's disease (AD). By studying postmortem tissue, researchers were able to identify gene expression changes associated with hippocampal vulnerability in AD, as well as genes related to AD neuropathology through machine learning. Further analysis suggested a relationship between SERPINA5 expression and tau expression in the brain.
NATURE COMMUNICATIONS
(2021)
Article
Veterinary Sciences
Ryo Imai, Rongduo Wen, Kaixin Li, Borjigin Sumiya, Hirofumi Matsumura, Tsuneyuki Masuda, Takuji Ozawa, Mami Oba, Shinji Makino, Makoto Nagai, Tetsuya Mizutani
Summary: Thirteen novel type 2 recombinant enterovirus G (EV-G) genomes were identified from several pig farms in Japan. Previously, type 2 recombinant EV-G had only been detected in neonatal piglets. These findings suggest that type 2 recombinant EV-G replicates in weaning piglets and sows. The detection of type 1 recombinant EV-Gs and type 2 recombinant EV-Gs at 3-year and 2-year intervals, respectively, from the same pig farm suggests persistent infection or circulation of the viruses in these farms.
JOURNAL OF VETERINARY MEDICAL SCIENCE
(2023)
Article
Chemistry, Organic
David R. Williams, Andrew F. Donnell, David C. Kammler, Sarah A. Ward, Levin Taylor
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Andrew F. Donnell, Paul J. Dollings, John A. Butera, Arlene J. Dietrich, Kerri K. Lipinski, Afshin Ghavami, Warren D. Hirst
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Robert F. Kester, Andrew F. Donnell, Yan Lou, Stacy W. Remiszewski, Louis J. Lombardo, Shaoqing Chen, Nam T. Le, Jennifer Lo, John A. Moliterni, Xiaochun Han, J. Heather Hogg, Weiling Liang, Christophe Michoud, Kenneth C. Rupert, Steven Mischke, Kang Le, Martin Weisel, Cheryl A. Janson, Christine M. Lukacs, Adrian J. Fretland, Kyoungja Hong, Ann Polonskaia, Lin Gao, Shirley Li, Dave S. Solis, Doug Aguilar, Christine Tardell, Mark Dvorozniak, Shahid Tannu, Edmund C. Lee, Andy D. Schutt, Barry Goggin
JOURNAL OF MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Medicinal
Yong Zhang, Yufen Zhao, Andrew J. Tebben, Steven Sheriff, Max Ruzanov, Mark P. Fereshteh, Yi Fan, Jonathan Lippy, Jesse Swanson, Ching-Ping Ho, Barri S. Wautlet, Anne Rose, Karen Parrish, Zheng Yang, Andrew F. Donnell, Liping Zhang, Brian E. Fink, Gregory D. Vite, Karen Augustine-Rauch, Joseph Fargnoli, Robert M. Borzilleri
ACS MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Yong Zhang, Karen E. Parrish, David R. Tortolani, Michael A. Poss, Audris Huang, Honghe Wan, Ashok Purandare, Andrew F. Donnell, James Kempson, Xiaoping Hou, Joseph Pawluczyk, Shiuhang Yip, Emily Luk, Nimmi Raghavan, Jesse Swanson, James Smalley, Anwar Murtaza, Zheng Yang, Karen Augustine-Rauch, Louis J. Lombardo, Robert Borzilleri
Summary: In mouse models, inhibition of TGF beta signaling in combination with checkpoint blockade has been shown to enhance and sustain antitumor immune response. To improve the therapeutic index, tumor-activated prodrugs of a selective small molecule TGF beta R1 inhibitor were developed, selectively metabolized in tumor tissues and reducing systemic exposure of the active drug.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Anthony N. Cauley, Antonio Ramirez, Chandan L. Barhate, Andrew F. Donnell, Purnima Khandelwal, Melda Sezen-Edmonds, Trevor C. Sherwood, Jack L. Sloane, Cullen L. Cavallaro, Eric M. Simmons
Summary: By utilizing quinoline as a mild catalytic additive, a broadly applicable method for Ni/photoredox-catalyzed C(sp(2))-C(sp(3)) cross-coupling was developed, which can be used in both batch and flow reactions. The method is effective for both primary benzylic nucleophiles and stabilized/nonstabilized secondary alkyl boronic esters.
Article
Chemistry, Multidisciplinary
Chandan L. Barhate, Andrew F. Donnell, Merrill Davies, Ling Li, Yong Zhang, Fukang Yang, Regina Black, Greg Zipp, Yingru Zhang, Cullen L. Cavallaro, E. Scott Priestley, Harold N. Weller
Summary: The successful miniaturization of assays in recent years has enabled the exploration of reducing synthesis scale in pharmaceutical discovery, leading to lower material consumption and shorter timelines without sacrificing data quality. Isolating and purifying compounds is a key step in library synthesis, and an optimized microscale purification system can efficiently purify samples.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Andrew F. Donnell, Yong Zhang, Erik M. Stang, Donna D. Wei, Andrew J. Tebben, Heidi L. Perez, Gretchen M. Schroeder, Chin Pan, Chetana Rao, Robert M. Borzilleri, Gregory D. Vite, Sanjeev Gangwar
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Multidisciplinary
DR Williams, DC Kammler, AF Donnell, WRF Goundry
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2005)
Article
Chemistry, Organic
DR Williams, AF Donnell, DC Kammler