Review
Immunology
Lars Hellman, Srinivas Akula, Zhirong Fu, Sara Wernersson
Summary: Proteases stored in mast cells have multiple functions, including maintaining connective tissue homeostasis, regulating blood pressure, and exhibiting anticoagulant activity. They can also modulate immune responses and provide protection against ectoparasites.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Gordon J. Lockbaum, Linah N. Rusere, Mina Henes, Klajdi Kosovrasti, Desaboini Nageswara Rao, Ean Spielvogel, Sook-Kyung Lee, Ellen A. Nalivaika, Ronald Swanstrom, Nese Kurt Yilmaz, Celia A. Schiffer, Akbar Ali
Summary: Protease inhibitors are powerful antivirals against HIV-1, but their effectiveness is reduced against resistant variants. Enhancing resistance profiles is crucial for developing more robust inhibitors, which could be promising for simplified next-generation antiretroviral therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Srinivas Akula, Zhirong Fu, Sara Wernersson, Lars Hellman
Summary: The chymase locus in mammals encodes multiple protease genes and has undergone expansions during evolution, with different species showing variations in gene numbers and specificities which may affect immune functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Alice-Roza Eruera, Alice M. McSweeney, Geena M. McKenzie-Goldsmith, Helen K. Opel-Reading, Simone X. Thomas, Ashley C. Campbell, Louise Stubbing, Andrew Siow, Jonathan G. Hubert, Margaret A. Brimble, Vernon K. Ward, Kurt L. Krause
Summary: Norovirus is a major cause of viral gastroenteritis worldwide. This study provides new insights for drug design against GII.4 genogroup of noroviruses.
Article
Pharmacology & Pharmacy
Shuang Liu, Yasuyuki Suzuki, Erika Takemasa, Ryusuke Watanabe, Masaki Mogi
Summary: This study investigated the role of mast cells in the response to SARS-CoV-2 viral inoculation and their contribution to host defenses. The results showed that mast cell stabilizers and chymase inhibitors have potential inhibitory effects on viral entry. Mast cell deficiency may increase the risk of viral invasion into the lower respiratory system.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Arun K. Ghosh, Dana Shahabi, Maya Kipfmiller, Ajay K. Ghosh, Megan Johnson, Yuan -Fang Wang, Johnson Agniswamy, Masayuki Amano, Irene T. Weber, Hiroaki Mitsuya
Summary: In this study, darunavir derived HIV-1 protease inhibitors were synthesized and evaluated for their biological activity. Modification of the P2' 4-amino functionality led to the development of amide derivatives that interacted with residues in the S2' subsite of the protease active site. Some compounds exhibited potent enzyme inhibitory and antiviral activity. X-ray crystallography revealed the binding mode of a chloroacetate derivative to the protease, showing enhanced hydrogen bonding interactions with the backbone atoms in the S2'-subsite.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Johnson Agniswamy, Daniel W. Kneller, Arun K. Ghosh, Irene T. Weber
Summary: The emergence of multidrug resistant HIV strains has severely reduced the effectiveness of antiretroviral therapy, making antiviral inhibitors targeting MDR proteases valuable as therapeutic agents. Substituted inhibitors derived from clinical inhibitor darunavir show significantly improved inhibition of drug resistant variants, providing potential for new treatment options.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Lucas Vellasco, Erik Svensjo, Carlos Alberto Bulant, Pablo Javier Blanco, Fabio Nogueira, Gilberto Domont, Natalia Pinto de Almeida, Clarissa Rodrigues Nascimento, Danielle Silva-dos-Santos, Carla Eponina Carvalho-Pinto, Emiliano Horacio Medei, Igor C. Almeida, Julio Scharfstein
Summary: Microangiopathy may worsen the clinical outcome of Chagas disease. This study used intravital microscopy to investigate microcirculatory alterations in the hamster cheek pouch infected by GFP-expressing T. cruzi. The findings suggest that intracellular amastigotes stimulate angiogenesis and enhance the delivery of plasma-borne nutrients and factors, benefiting the host-parasite relationship.
Article
Chemistry, Medicinal
Kenji Nakahara, Yasunori Mitsuoka, Satoshi Kasuya, Takahiko Yamamoto, Shiho Yamamoto, Hisanori Ito, Yasuto Kido, Ken-ichi Kusakabe
Summary: This report details the discovery of BACE1 inhibitors with a 1-amino-3,4-dihydro-2,6-naphthyridine scaffold, which showed improved biochemical and cellular potency with reduced basicity. A compound with a fluorine atom on the pyridine ring demonstrated enhanced cellular activity and sustained cerebrospinal fluid A beta reduction in dog models, confirmed by crystal structure analysis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Patrycja Kwiecinska, Mateusz Kwitniewski, Kamila Kwiecien, Agnieszka Morytko, Pawel Majewski, Natalia Pocalun, Maciej Pastuszczak, Marcin Migaczewski, Joanna Cichy, Beata Grygier
Summary: This study investigated the role of secretory leukocyte protease inhibitor (SLPI) in mast cell-dependent processes and found that SLPI inhibits the activity of chymase in mast cells and enhances their degranulation. The study also showed that SLPI is expressed in dermal mast cells of patients with psoriasis. These findings reveal previously unknown mechanisms underlying FceRI and Mrgprb2-dependent mast cell function.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yudai Imai, Ryo Suzuki, Daisuke Wakasugi, Daisuke Matsuda, Nozomi Tanaka-Yamamoto, Yuta Ohki, Masashi Mima, Mayumi Endo, Ryotaro Tabata, Hitomi Matsuzawa, Yoshitaka Hasegawa, Sota Kato, Mami Sugisaki, Hiroh Miyagawa, Natsuko Fujimoto, Takuya Fukunaga, Sayaka Kato, Teisuke Takahashi, Hiroyuki Kakinuma
Summary: HPSE1 is an enzyme that cleaves heparan sulfate in the vascular matrix. Inhibiting HPSE1 has therapeutic potential for cancer and kidney diseases. Compound 18 is a novel HPSE1 inhibitor with improved potency.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Catherine Lapointe, Laurence Vincent, Hugo Giguere, Mannix Auger-Messier, Adel Schwertani, Denan Jin, Shinji Takai, Gunnar Pejler, Martin G. G. Sirois, Hanna Tinel, Stefan Heitmeier, Pedro D'Orleans-Juste
Summary: Deep vein thrombosis (DVT) is a major cause of pulmonary embolism and a life-threatening cardiovascular disease. Current anticoagulants have limitations in treating DVT due to their effects on bleeding time. This study identifies the crucial role of a protease called mMCP-4 in DVT formation and suggests a novel strategy to resolve or prevent DVT by inhibiting mMCP-4.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Biochemistry & Molecular Biology
Alena I. Krysantieva, Julia K. Voronina, Damir A. Safin
Summary: A novel 1,2,3,4-tetrahydroquinazoline derivative, 2-(6,8-dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl)phenol (1), was synthesized from ambroxol hydrochloride and salicylaldehyde. The compound formed colorless crystals of 1 center dot 0.5EtOH composition. Characterization was performed using IR spectroscopy, H-1 spectroscopy, single-crystal and powder X-ray diffraction, and elemental analysis. UV-vis spectroscopy revealed the compound's absorption in the UV region up to about 350 nm in MeOH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tatiana F. R. Costa, Amy Goundry, Alexandre Morrot, Dennis J. Grab, Jeremy C. Mottram, Ana Paula C. A. Lima
Summary: This study reveals the mechanism of Trypanosoma brucei rhodesiense penetration through the blood-brain barrier and causing sleeping sickness. The Cathepsin L-like cysteine peptidase and its endogenous inhibitor ICP play important roles in the infection process and regulate inflammatory responses. The results suggest that ICP helps to downregulate inflammatory responses and control the infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaobin Fang, Mengmeng Li, Weiyi Zhang, Jingyi Li, Tao Zhu
Summary: Thrombin-induced mast cell activation results in the production of both pro- and anti-inflammatory mediators, involving the expression of PAR1 and PAR4 as well as activation of MAPK signaling pathways. Dual activation of mast cells occurs after thrombin stimulation.
MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paul D. Adams, Kathleen Aertgeerts, Cary Bauer, Jeffrey A. Bell, Helen M. Berman, Talapady N. Bhat, Jeff M. Blaney, Evan Bolton, Gerard Bricogne, David Brown, Stephen K. Burley, David A. Case, Kirk L. Clark, Tom Darden, Paul Emsley, Victoria A. Feher, Zukang Feng, Colin R. Groom, Seth F. Harris, Jorg Hendle, Thomas Holder, Andrzej Joachimiak, Gerard J. Kleywegt, Tobias Krojer, Joseph Marcotrigiano, Alan E. Mark, John L. Markley, Matthew Miller, Wladek Minor, Gaetano T. Montelione, Garib Murshudov, Atsushi Nakagawa, Haruki Nakamura, Anthony Nicholls, Marc Nicklaus, Robert T. Nolte, Anil K. Padyana, Catherine E. Peishoff, Susan Pieniazek, Randy J. Read, Chenghua Shao, Steven Sheriff, Oliver Smart, Stephen Soisson, John Spurlino, Terry Stouch, Radka Svobodova, Wolfram Tempel, Thomas C. Terwilliger, Dale Tronrud, Sameer Velankar, Suzanna C. Ward, Gregory L. Warren, John D. Westbrook, Pamela Williams, Huanwang Yang, Jasmine Young
Article
Biochemistry & Molecular Biology
Robert H. Scannevin, Richard Alexander, Tara Mezzasalma Haarlander, Sharon L. Burke, Monica Singer, Cuifen Huo, Yue-Mei Zhang, Diane Maguire, John Spurlino, Ingrid Deckman, Karen I. Carroll, Frank Lewandowski, Eric Devine, Keli Dzordzorme, Brett Tounge, Cindy Milligan, Shariff Bayoumy, Robyn Williams, Celine Schalk-Hihi, Kristi Leonard, Paul Jackson, Matthew Todd, Lawrence C. Kuo, Kenneth J. Rhodes
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Christian Gege, Maxwell D. Cummings, Michael Albers, Olaf Kinzel, Gerald Kleymann, Thomas Schlueter, Christoph Steeneck, Marina Nelen, Cindy Milligan, John Spurlino, Xiaohua Xue, Kristi Leonard, James P. Edwards, Anne Fourie, Steven D. Goldberg, Thomas Hoffmann
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Kevin D. Kreutter, Tianbao Lu, Lily Lee, Edward C. Giardino, Sharmila Patel, Hui Huang, Guozhang Xu, Mark Fitzgerald, Barbara J. Haertlein, Venkatraman Mohan, Carl Crysler, Stephen Eisennagel, Malini Dasgupta, Martin McMillan, John C. Spurlino, Norman D. Huebert, Bruce E. Maryanoff, Bruce E. Tomczuk, Bruce P. Damiano, Mark R. Player
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2008)
Article
Chemistry, Medicinal
Michael J. Costanzo, Stephen C. Yabut, Han-Cheng Zhang, Kimberley B. White, Lawrence de Garavilla, Yuanping Wang, Lisa K. Minor, Brett A. Tounge, Alexander N. Barnakov, Frank Lewandowski, Cynthia Milligan, John C. Spurlino, William M. Abraham, Victoria Boswell-Smith, Clive P. Page, Bruce E. Maryano
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2008)
Article
Chemistry, Medicinal
Gary Tresadern, Francisca Delgado, Oscar Delgado, Harrie Gijsen, Gregor J. Macdonald, Dieder Moechars, Frederik Rombouts, Richard Alexander, John Spurlino, Michiel Van Gool, Juan Antonio Vega, Andres A. Trabanco
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Medicinal
Tianbao Lu, Thomas Markotan, Shelley K. Ballentine, Edward C. Giardino, John Spurlino, Kathryn Brown, Bruce E. Maryanoff, Bruce E. Tomczuk, Bruce P. Damiano, Umesh Shukla, David End, Patricia Andrade-Gordon, Roger F. Bone, Mark R. Player
JOURNAL OF MEDICINAL CHEMISTRY
(2010)
Correction
Chemistry, Medicinal
Tianbao Lu, Thomas Markotan, Shelley K. Ballentine, Edward C. Giardino, John Spurlino, Carl S. Crysler, Kathryn Brown, Bruce E. Maryanoff, Bruce E. Tomczuk, Bruce P. Damiano, Umesh Shukla, David End, Patricia Andrade-Gordon, Roger F. Bone, Mark R. Player
JOURNAL OF MEDICINAL CHEMISTRY
(2010)
Article
Biochemistry & Molecular Biology
Marta C. Abad, Hossein Askari, John O'Neill, Alexandra L. Klinger, Cynthia Milligan, Frank Lewandowski, Barry Springer, John Spurlino, Dionisios Rentzeperis
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2008)
Article
Chemistry, Medicinal
Michael J. Costanzo, Stephen C. Yabut, Han-Cheng Zhang, Kimberley B. White, Yuanping Wang, Lisa K. Minor, Brett A. Tounge, Alexander N. Barnakov, Frank Lewandowski, Cynthia Milligan, John C. Spurlino, Bruce E. Maryanoff
LETTERS IN DRUG DESIGN & DISCOVERY
(2008)
Article
Chemistry, Medicinal
J. Kent Barbay, Maxwell D. Cummings, Marta Abad, Glenda Castro, Kevin D. Kreutter, David A. Kummer, Umar Maharoof, Cynthia Milligan, Rachel Nishimura, Joan Pierce, Celine Schalk-Hihi, John Spurlino, Virginia M. Tanis, Maud Urbanski, Hariharan Venkatesan, Aihua Wang, Craig Woods, Ronald Wolin, Xiaohua Xue, James P. Edwards, Anne M. Fourie, Kristi Leonard
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
David A. Kummer, Maxwell D. Cummings, Marta Abad, Joseph Barbay, Glenda Castro, Ronald Wolin, Kevin D. Kreutter, Umar Maharoof, Cynthia Milligan, Rachel Nishimura, Joan Pierce, Celine Schalk-Hihi, John Spurlino, Maud Urbanski, Hariharan Venkatesan, Aihua Wang, Craig Woods, Xiaohua Xue, James P. Edwards, Anne M. Fourie, Kristi Leonard
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
Lily Lee, Kevin D. Kreutter, Wenxi Pan, Carl Crysler, John Spurlino, Mark R. Player, Bruce Tomezuk, Tianbao Lu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2007)
Article
Biochemistry & Molecular Biology
Carsten Schubert, Celine Schalk-Hihi, Geoffrey T. Struble, Hong-Chang Ma, Ioanna P. Petrounia, Benjamin Brandt, Ingrid C. Deckman, Raymond J. Patch, Mark R. Player, John C. Spurlino, Barry A. Springer
JOURNAL OF BIOLOGICAL CHEMISTRY
(2007)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)