Article
Biochemistry & Molecular Biology
Lakshmanan Loganathan, Jeyanthi Sankar, Kannan Rajendran, Karthikeyan Muthusamy
Summary: The renin enzyme is an important target for treating hypertension and renal diseases, but there is currently no FDA-approved renin inhibitor. This study used theoretical and experimental approaches to identify potential renin inhibitors that are stable, active, and safe. These compounds may improve the efficacy of hypertension treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Shuvechha Chakraborty, Kshitija Rahate, Chandan Kumar, Susan Idicula-Thomas
Summary: This study systematically investigated the druggability of Candida proteome and discovered two SAP inhibitors that can significantly reduce the dosage of fluconazole required for Candida inhibition. Wet-lab validation confirmed their inhibitory activity on par with pepstatin A, a known inhibitor of aspartyl proteases.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Leandro Rocha Silva, Ari Souza Guimaraes, Jadiely do Nascimento, Igor Jose do Santos Nascimento, Elany Barbosa da Silva, James H. McKerrow, Silvia Helena Cardoso, Edeildo Ferreira da Silva-Junior
Summary: This study evaluated the structures of CRZ and RhD, identifying a potent inhibitory molecule. Through virtual screening and dynamic simulations, several promising inhibitors were found, with JN-11 showing time-dependent and reversible inhibition.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Douglas A. S. Grahame, John H. Dupuis, Brian C. Bryksa, Takuji Tanaka, Rickey Y. Yada
Summary: The study aimed to determine the structural determinants of aspartic protease stability and activity at high pH levels. It revealed that certain mutants showed increased activity and maintained native-like structure at elevated pH, concluding that reducing electrostatic repulsions and understanding the hydrogen bonding network of the characteristic 13-barrel are crucial for alkaline stabilization of pepsin.
ENZYME AND MICROBIAL TECHNOLOGY
(2021)
Article
Microbiology
Pavla Snebergerova, Pavla Bartosova-Sojkova, Marie Jalovecka, Daniel Sojka
Summary: Apicomplexan genomes encode multiple pepsin-family aspartyl proteases that have diversified to adapt to different strategies of host infection and transmission. Expressional profiling of Babesia microti APs and phylogenetic analysis of APs from selected Babesia and Theileria species indicate their potential roles and druggable enzymatic targets for specific therapy for babesiosis.
Article
Chemistry, Medicinal
Lachlan W. Richardson, Trent D. Ashton, Madeline G. Dans, Nghi Nguyen, Paola Favuzza, Tony Triglia, Anthony N. Hodder, Anna Ngo, Kate E. Jarman, Alan F. Cowman, Brad E. Sleebs
Summary: Plasmepsin X is an important aspartyl protease in the invasion and egression of Plasmodium parasites. In this study, peptidomimetics were designed to inhibit Plasmepsin X and effectively arrested the development of asexual Plasmodium falciparum parasites. These findings are significant for understanding the substrate specificity of Plasmepsin X and designing future antimalarial drugs.
Review
Peripheral Vascular Disease
Melisande L. Addison, Priyanga Ranasinghe, David J. Webb
Summary: Hypertension, affecting half of US adults, is the leading cause of cardiovascular disease and premature death globally. Novel pharmacological strategies that silences liver angiotensinogen have shown impressive and durable effects on blood pressure control.
Article
Chemistry, Medicinal
Laura J. Kingsley, Xiaohui He, Matthew McNeill, John Nelson, Victor Nikulin, Zhiwei Ma, Wenshuo Lu, Vicki W. Zhou, Mari Manuia, Andreas Kreusch, Mu-Yun Gao, Darbi Witmer, Mei-Ting Vaillancourt, Min Lu, Sarah Greenblatt, Christian Lee, Ajay Vashisht, Steven Bender, Glen Spraggon, Pierre-Yves Michellys, Yong Jia, Jacob R. Haling, Gerald Lelais
Summary: LONP1 is an AAA+ protease essential for maintaining mitochondrial homeostasis, with its inhibitors potentially promoting cancer cell proliferation. This study describes the development of selective boronic acid-based LONP1 inhibitors and the structures of human LONP1 in complex with various inhibitors, providing valuable tools for investigating LONP1 biology.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Kody A. Klupt, Zongchao Jia
Summary: The alpha-kinase eEF2K phosphorylates eEF2 at its threonine 56 residue to inhibit protein translation. Investigation into eEF2K targeting involves structure-based drug design using computational techniques. eEF2K plays diverse roles in diseases like cancer and neurological disorders, and inhibiting it is considered a potential treatment option. This review discusses the use of homology modeling with crystal structures of related alpha-kinases to improve inhibitor design, as well as the history of eEF2K-related drug discovery and future prospects with the availability of eEF2K crystal structure.
Article
Biochemistry & Molecular Biology
Hai Ping Shao, Tian Hua Wang, Hong Lin Zhai, Ke Xin Bi, Bing Qiang Zhao
Summary: In this study, the interaction mechanisms of two representative peptide inhibitors (11a and PF-07321332) with SARS-CoV-2 main protease (Mpro) were investigated for the first time using molecular dynamics simulation. Fragment-based drug design method was then employed to select fragments from existing SARS-CoV and SARS-CoV-2 inhibitors to replace the original P2 and P3 fragments, resulting in new molecules. Molecular docking, molecular dynamics simulation, and ADMET properties prediction confirmed the excellent activity and physicochemical properties of two molecules (O-74 and N-98), suggesting their potential as new inhibitors for SARS-CoV-2 main protease.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Murtala A. Ejalonibu, Segun A. Ogundare, Ahmed A. Elrashedy, Morufat A. Ejalonibu, Monsurat M. Lawal, Ndumiso N. Mhlongo, Hezekiel M. Kumalo
Summary: Developing new antibiotics targeting resistant Mycobacterium tuberculosis is an appealing strategy to combat the global tuberculosis epidemic, with computational techniques playing a key role in drug design and discovery. Recent advancements in technology have enhanced the chances of drug development, offering hope in the fight against tuberculosis resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Article
Allergy
Ahmed O. Shalash, Luke Becker, Jieru Yang, Paul Giacomin, Mark Pearson, Waleed M. Hussein, Alex Loukas, Istvan Toth, Mariusz Skwarczynski
Summary: This study compared the protective efficacy of peptide vaccines and a clinical vaccine, and found that peptide vaccines based on p3 provided safer and higher protection against hookworm infection compared with the clinical vaccine Na-APR-1.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Engineering, Chemical
Mahmoud A. El Hassab, Mohamed Fares, Mohammed K. Abdel-Hamid Amin, Sara T. Al-Rashood, Amal Alharbi, Razan O. Eskandrani, Hamad M. Alkahtani, Wagdy M. Eldehna
Summary: The outbreak of the COVID-19 pandemic has created an urgent need for new medication. This study focused on the development of a potential inhibitor for the SARS-CoV-2 Mpro enzyme through structure-based drug design. The designed compound RMH148 showed promising interactions with the enzyme and stability at the active site.
Editorial Material
Medicine, Research & Experimental
Keiichi Torimoto, Satoru Eguchi
Summary: The study highlights the role of sPRR as a ligand for AT1R, causing endothelial dysfunction and hypertension. The interaction between sPRR and AT1R contributes to obesity-induced cardiovascular diseases. The sPRR/AT1R complex may be a potential therapeutic target for endothelial dysfunction.
Article
Biochemistry & Molecular Biology
Stephen D. Lotesta, Andrew P. Marcus, Yajun Zheng, Katerina Leftheris, Paul B. Noto, Shi Meng, Geeta Kandpal, Guozhou Chen, Jing Zhou, Brian McKeever, Yuri Bukhtiyarov, Yi Zhao, Deepak S. Lala, Suresh B. Singh, Gerard M. McGeehan
BIOORGANIC & MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Colin M. Tice, Ya-Jun Zheng
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Medicinal
Colin M. Tice, Paul B. Noto, Kristi Yi Fan, Wei Zhao, Stephen D. Lotesta, Chengguo Dong, Andrew P. Marcus, Ya-Jun Zheng, Guozhou Chen, Zhongren Wu, Rebecca Van Orden, Jing Zhou, Yuri Bukhtiyarov, Yi Zhao, Kerri Lipinski, Lamont Howard, Joan Guo, Geeta Kandpal, Shi Meng, Andrew Hardy, Paula Krosky, Richard E. Gregg, Katerina Leftheris, Brian M. McKeever, Suresh B. Singh, Deepak Lala, Gerard M. McGeehan, Linghang Zhuang, David A. Claremon
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Editorial Material
Pharmacology & Pharmacy
Ya-Jun Zheng, Colin M. Tice
EXPERT OPINION ON DRUG DISCOVERY
(2016)
Article
Chemistry, Medicinal
Yajun Zheng, Linghang Zhuang, Kristi Yi Fan, Colin M. Tice, Wei Zhao, Chengguo Dong, Stephen D. Lotesta, Katerina Leftheris, Peter R. Lindblom, Zhijie Liu, Jun Shimada, Paul B. Noto, Shi Meng, Andrew Hardy, Lamont Howard, Paula Krosky, Joan Guo, Kerri Lipinski, Geeta Kandpal, Yuri Bukhtiyarov, Yi Zhao, Deepak Lala, Rebecca Van Orden, Jing Zhou, Guozhou Chen, Zhongren Wu, Brian M. McKeever, Gerard M. McGeehan, Richard E. Gregg, David A. Claremon, Suresh B. Singh
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Yajun Zheng, Colin M. Tice, Suresh B. Singh
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Colin M. Tice, Paul B. Noto, Kristi Yi Fan, Linghang Zhuang, Deepak S. Lala, Suresh B. Singh
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Chemistry, Medicinal
Jason M. Rohde, Surendra Karavadhi, Rajan Pragani, Li Liu, Yuhong Fang, Weihe Zhang, Andrew McIver, Hongchao Zheng, Qingyang Liu, Mindy Davis, Daniel J. Urban, Tobie D. Lee, Dorian M. Cheff, Melinda Hollingshead, Mark J. Henderson, Natalia J. Martinez, Kyle R. Brimacombe, Adam Yasgar, Wei Zhao, Carleen Klumpp-Thomas, Sam Michael, Joseph Covey, William J. Moore, Gordon M. Stott, Zhuyin Li, Anton Simeonov, Ajit Jadhav, Stephen Frye, Matthew D. Hall, Min Shen, Xiaodong Wang, Samarjit Patnaik, Matthew B. Boxer
Summary: The research focused on neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) and led to the discovery of a series of potent mIDH1 inhibitors, including the atropisomer (+)-119, which showed higher tumoral concentrations and lower 2-HG concentrations in an engineered mouse model compared to the approved drug AG-120.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Lei Shi, William Shen, Mindy I. Davis, Ke Kong, Phuong Vu, Supriya K. Saha, Ramzi Adil, Johannes Kreuzer, Regina Egan, Tobie D. Lee, Patricia Greninger, Jonathan H. Shrimp, Wei Zhao, Ting-Yu Wei, Mi Zhou, Jason Eccleston, Jonathan Sussman, Ujjawal Manocha, Vajira Weerasekara, Hiroshi Kondo, Vindhya Vijay, Meng-Ju Wu, Sara E. Kearney, Jeffrey Ho, Joseph McClanaghan, Ellen Murchie, Giovanna S. Crowther, Samarjit Patnaik, Matthew B. Boxer, Min Shen, David T. Ting, William Y. Kim, Ben Z. Stanger, Vikram Deshpande, Cristina R. Ferrone, Cyril H. Benes, Wilhelm Haas, Matthew D. Hall, Nabeel Bardeesy
Summary: In this study, the researchers identified the vulnerability of liver tumors expressing the sulfotransferase SULT1A1 and found that they are sensitive to the small molecule YC-1 and other structurally related compounds. This discovery provides a basis for the preclinical development of these agents and highlights the potential of targeting SULT1A1 activity for selective treatments.
Article
Biochemistry & Molecular Biology
Linghang Zhuang, Colin M. Tice, Zhenrong Xu, Wei Zhao, Salvacion Cacatian, Yuan-Jie Ye, Suresh B. Singh, Peter Lindblom, Brian M. McKeever, Paula M. Krosky, Yi Zhao, Deepak Lala, Barbara A. Kruk, Shi Meng, Lamont Howard, Judith A. Johnson, Yuri Bukhtiyarov, Reshma Panemangalore, Joan Guo, Rong Guo, Frank Himmelsbach, Bradford Hamilton, Annette Schuler-Metz, Heike Schauerte, Richard Gregg, Gerard M. McGeehan, Katerina Leftheris, David A. Claremon
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Meeting Abstract
Dermatology
Y. Zhao, S. Meng, P. B. Noto, K. K. Lipinski, Y. E. Bukhtiyarov, L. Zhuang, C. Tice, W. Zhao, C. Dong, S. Lotesta, A. Marcus, K. Leftheris, Y. Zheng, K. Fan, S. B. Singh, D. Claremon, G. M. McGeehan, D. Lala
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2015)
Meeting Abstract
Chemistry, Multidisciplinary
Zhijie Liu, Peter Lindblom, Yuanjie Ye, Colin Tice, Linghang Zhuang, Wei Zhao, Katerina Leftheris, Barbara Kruk, Paula Krosky, Deepak Lala, Gerard McGeehan, David Claremon, Richard Gregg, Suresh B. Singh
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2012)
