Review
Chemistry, Multidisciplinary
Ke Li, Craig M. Crews
Summary: PROTACs are a type of molecules with novel event-driven mechanism, offering multiple advantages over traditional inhibitors, such as catalytic nature and targeted protein degradation, which may lead to improved therapeutic outcomes with reduced toxicity. However, further research and development efforts are needed to fully explore their potential.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Biochemical Research Methods
Abhijit Tarafder, Larry Miller
Summary: Method screening is a crucial step in chromatographic method development for separating racemates. Various solutions and strategies have been proposed over the years to reduce the time spent on method screening, with some being adopted in practice and others remaining in academic literature. The main objective of this review is to revisit and compile the diverse set of solutions published in the last two decades for evaluating the adequacy of existing screening protocols in laboratories conducting chiral separations.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Review
Cell Biology
Michael A. Cook, Gerard D. Wright
Summary: Antibiotics have played a crucial role in modern medicine, but they are facing challenges of microbial resistance and traditional reimbursement models. Therefore, innovation is needed in policy, quantitative understanding of societal value, and investment in alternatives. Significant investment in research and development is also necessary to address the antibiotic crisis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Materials Science, Multidisciplinary
Joseph Rich, Zhenhua Tian, Tony Jun Huang
Summary: The research in intracellular delivery technologies has surged with the advancement in cell-based therapies and reprogramming. Physical cell membrane permeabilization techniques, especially sonoporation, show promise in delivering functional cargos to various cells, but bubble-based methods may have limitations such as requiring contrast agents and potential damage to cell components. Development of non-bubble-based sonoporation mechanisms aims to overcome these limitations and improve intracellular delivery efficiency.
ADVANCED MATERIALS TECHNOLOGIES
(2022)
Review
Chemistry, Multidisciplinary
Wentao Jiang, Ziyu Wu, Zheng Gao, Mimi Wan, Min Zhou, Chun Mao, Jian Shen
Summary: Artificial cells are constructed to imitate natural cells and can be used for studying biological processes and the origin of life. They can be endowed with various functions through the incorporation of proteins and genes, and have great potential in therapeutic applications.
Review
Chemistry, Multidisciplinary
Sameek Singh, Wenzhi Tian, Zachary C. Severance, Santosh K. Chaudhary, Viktoriya Anokhina, Basudeb Mondal, Rajaiah Pergu, Prashant Singh, Uttam Dhawa, Santanu Singha, Amit Choudhary
Summary: Living systems regulate biochemical processes through proximity. Inspired by this, bifunctional modalities have been developed to redirect cellular processes. An emerging example is molecules that induce ubiquitin-dependent proteasomal degradation of a protein of interest, sparking discovery for other bifunctional modalities. Recent advances include modalities that can change protein phosphorylation, glycosylation, and acetylation states, modulate gene expression, and recruit components of the immune system. This review highlights non-degradation bifunctional modalities with potential to revolutionize disease treatment and explore new aspects of biology in basic research.
CHEMICAL SOCIETY REVIEWS
(2023)
Review
Chemistry, Medicinal
Yasuhiro Nishida, Pernilla Christina Berg, Behnaz Shakersain, Karen Hecht, Akiko Takikawa, Ruohan Tao, Yumeka Kakuta, Chiasa Uragami, Hideki Hashimoto, Norihiko Misawa, Takashi Maoka
Summary: This review article provides a comprehensive exploration of the history, chemical and physical attributes, distribution, and biosynthesis of astaxanthin (AX). It also delves into the health benefits, biofunctional characteristics, and market status of AX, aiming to provide a robust foundation for future scientific endeavors addressing societal needs for sustainable nutritional and medicinal solutions.
Review
Plant Sciences
Ian Max Moller, Allan G. Rasmusson, Olivier Van Aken
Summary: The study of plant mitochondria began in the 1950s, focusing on establishing basic properties and unique characteristics compared to mammalian mitochondria. With advancements in molecular biology and genomics, further unique features were discovered, including the large size of plant mtDNA, unique mRNA maturation process, and a large proteome with many unique proteins.
Article
Immunology
Shubham Upadhayay, Richmond Arthur, Divya Soni, Poonam Yadav, UmaShanker Navik, Randhir Singh, Thakur Gurjeet Singh, Puneet Kumar
Summary: Monkeypox is a zoonotic disease similar to smallpox, transmitted through direct contact with infected animals or individuals with infectious sores, scabs, or body fluids. There is currently no definitive treatment, but antiviral medication can be used to alleviate symptoms and reverse skin lesions.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Xiaozhou Ma, Jelco Albertsma, Dieke Gabriels, Rens Horst, Sevgi Polat, Casper Snoeks, Freek Kapteijn, Huseyin Burak Eral, David A. A. Vermaas, Bastian Mei, Sissi de Beer, Monique Ann van der Veen
Summary: Large amounts of carbon monoxide are produced through industrial processes, but separating carbon monoxide from other gases is challenging due to their similar physical properties. However, carbon monoxide is valuable in the production of chemicals and hydrocarbons, making the development of efficient CO separation processes important for both industry and the environment.
CHEMICAL SOCIETY REVIEWS
(2023)
Review
Chemistry, Multidisciplinary
Yungyeong Lee, Cyrille Boyer, Min Sang Kwon
Summary: In this review, the history, progress, and applications of photocontrolled reversible addition-fragmentation chain transfer (RAFT) polymerization are briefly summarized. The challenges of this technique, including photoinduced electron/energy transfer-RAFT (PET-RAFT), photoiniferter, and photomediated cationic RAFT polymerization, are discussed. Visible-light-driven RAFT polymerization has gained significant attention due to its low energy consumption and safe reaction procedure, and the use of visible-light photocatalysis offers additional benefits such as spatiotemporal control and oxygen tolerance. However, a comprehensive understanding of the reaction mechanism is still lacking. Recent efforts combining quantum chemical calculations and experimental evidence have been made to elucidate the polymerization mechanisms. This review provides insights for the better design of polymerization systems and explores the full potential of photocontrolled RAFT polymerization in both academic and industrial applications.
CHEMICAL SOCIETY REVIEWS
(2023)
Review
Chemistry, Multidisciplinary
Xinxin Wu, Zhigang Ma, Tingting Feng, Chen Zhu
Summary: Rearrangement reactions are crucial in organic chemistry, improving synthetic efficiency and molecular complexity. Ionic rearrangement reactions and radical-mediated rearrangements are the focus of research, with new radical rearrangements revealing migratory behavior of functional groups.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Neurosciences
Marcela Lipovsek, Cedric Bardy, Cathryn R. Cadwell, Kristen Hadley, Dmitry Kobak, Shreejoy J. Tripathy
Summary: Patch-seq is a revolutionary technique in neuroscience that integrates morphology, physiology, and gene expression data to study neuronal biology comprehensively. It enables targeted study of specific neuronal populations, compilation of multimodal cell type atlases, and investigation of the molecular basis of morphologic and functional diversity. This technique has the potential for further technical development and implementation in various research areas to directly link gene expression to brain function.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Physics, Particles & Fields
Nathaniel Craig
Summary: This article assesses the state of naturalness in high-energy physics and summarizes recent approaches to the three major naturalness problems: the cosmological constant problem, the electroweak hierarchy problem, and the strong CP problem.
EUROPEAN PHYSICAL JOURNAL C
(2023)
Editorial Material
Engineering, Electrical & Electronic
Manuel Cebrian
Summary: Digital contact tracing technology has been quietly explored for over a decade before the COVID-19 pandemic brought it into the spotlight. However, its effectiveness in the complexity of real-world social networks remains a topic of debate.
NATURE ELECTRONICS
(2021)
Editorial Material
Chemistry, Medicinal
Jonathan B. Baell
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sarah Preston, Jose Garcia-Bustos, Liam G. Hall, Sheree D. Martin, Thuy G. Le, Abhijit Kundu, Atanu Ghoshal, Nghi H. Nguyen, Yaqing Jiao, Banfeng Ruan, Lian Xue, Fei Huang, Bill C. H. Chang, Sean L. McGee, Timothy N. C. Wells, Michael J. Palmer, Abdul Jabbar, Robin B. Gasser, Jonathan B. Baell
Summary: A series of novel compounds were synthesized as potent inhibitors of Haemonchus contortus, the parasitic nematode of sheep, showing high selectivity in mammalian cell lines but causing acute toxicity in rodents, possibly due to respiratory inhibition. Additionally, potent cytotoxicity was observed in rat hepatocytes, unrelated to toxicity in respiring cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Daniel L. Priebbenow, Mitch Mathiew, Da-Hua Shi, Jitendra R. Harjani, Julia G. Beveridge, Marina Chavchich, Michael D. Edstein, Sandra Duffy, Vicky M. Avery, Robert T. Jacobs, Stephen Brand, David M. Shackleford, Wen Wang, Longjin Zhong, Given Lee, Erin Tay, Helena Barker, Elly Crighton, Karen L. White, Susan A. Charman, Amanda De Paoli, Darren J. Creek, Jonathan B. Baell
Summary: A series of novel 3,3'-disubstituted-5,5'-bi(1,2,4-triazine) compounds with potent in vitro activity against Plasmodium falciparum parasites were recently discovered. The new structure-activity relationship investigation led to the identification of second-generation highly potent antimalarial bis-triazines, with improved in vitro metabolic stability and a fast-killing profile. This new class of orally available antimalarial compounds is of considerable interest.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Michael J. Roy, Amelia Vom, Toru Okamoto, Brian J. Smith, Richard W. Birkinshaw, Hong Yang, Houda Abdo, Christine A. White, David Segal, David C. S. Huang, Jonathan B. Baell, Peter M. Colman, Peter E. Czabotar, Guillaume Lessene
Summary: The BCL-2 family of proteins is an important target for anticancer drug development, with inhibitors like ABT-199/vebetoclax showing transformative effects. Developing new validated chemical series for BCL-X-L is desirable.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Katherine M. Ellis, Leonardo Lucantoni, Marina Chavchich, Matthew Abraham, Amanda De Paoli, Madeline R. Luth, Anne-Marie Zeeman, Michael J. Delves, Fernando Sanchez-Roman Teran, Ursula Straschil, Jake Baum, Clemens H. M. Kocken, Stuart A. Ralph, Elizabeth A. Winzeler, Vicky M. Avery, Michael D. Edstein, Jonathan B. Baell, Darren J. Creek
Summary: Novel bis-1,2,4-triazine compound MIPS-0004373 demonstrates potent in vitro activity against Plasmodium falciparum parasites, with good efficacy against blood and sexually committed ring stage parasites. The compound also shows activity against liver stage parasites in an in vitro P. berghei model, but limited activity against mature gametocytes. In vivo, MIPS-0004373 efficiently clears established P. berghei infection, with efficacy similar to artesunate and chloroquine.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Noel P. Pitcher, Jitendra R. Harjani, Yichao Zhao, Jianwen Jin, Daniel R. Knight, Lucy Li, Papanin Putsathit, Thomas Riley, Glen P. Carter, Jonathan B. Baell
Summary: Colonization of pathogenic bacteria in the GI tract is a significant risk factor for healthcare-associated infections. Efforts to develop effective decolonization agents have been largely unsuccessful. This study modified antimicrobial compounds to target bacterial pathogens in the GI tract and identified potential candidates for further development of colon-targeted antimicrobial agents.
Article
Biochemistry & Molecular Biology
Ashley J. Ovens, Yi Sing Gee, Naomi X. Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung, Kevin R. W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf
Summary: AMPK is a cellular energy sensor and regulator of energy homeostasis. Activating AMPK shows potential for treating type 2 diabetes and insulin resistance. Recent studies suggest that the ??202??1 isoform combination is primarily responsible for these effects. Structure/function analysis of SC4 activator led to the discovery of MSG010 and MSG011, which show greater potency in activating ??202??1 AMPK compared to MK-8722. These findings guide the development of selective AMPK activators.
BIOCHEMICAL JOURNAL
(2022)
Article
Chemistry, Medicinal
Lisa Barbaro, Gayathri Nagalingam, James A. Triccas, Lendl Tan, Nicholas P. West, Daniel L. Priebbenow, Jonathan B. Baell
Summary: The clinical use of bedaquiline has been limited due to safety concerns. Recent investigations have found that modification of the B- and C-ring units of bedaquiline can lead to the development of new compounds with potent anti-tubercular activity but improved safety. Concurrent modification of the A-, B-, and C-ring units in bedaquiline variants has been shown to result in compounds with relatively potent anti-tubercular activity and reduced safety issues.
Article
Chemistry, Medicinal
Nicole McNamara, Eleanor Saunders, Swapna Varghese, Rebecca Zheng, Kaylene Simpson, Devika M. Varma, Monica M. Johnson, M. Shamim Hasan Zahid, Eric M. Bachelder, Kristy M. Ainslie, Joo Hwan No, Dahae Koh, David Shum, Nirmal Das, Binita Patra, Jayasree Roy, Arindam Talukdar, Dipyman Ganguly, Malcolm McConville, Jonathan Baell
Summary: In this study, the structure-activity relationship of a novel hit compound was explored. The compound showed improved potency with low cytotoxicity against human cells, indicating its potential as a treatment for visceral leishmaniasis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Victoria Y. Ling, Jasmin Straube, William Godfrey, Rohit Haldar, Yashaswini Janardhanan, Leanne Cooper, Claudia Bruedigam, Emily Cooper, Paniz Tavakoli Shirazi, Sebastien Jacquelin, Siok-Keen Tey, Jonathan Baell, Fei Huang, Jianwen Jin, Yichao Zhao, Lars Bullinger, Megan J. Bywater, Steven W. Lane
Summary: This study identifies defective cell cycle arrest as a clinically relevant contributor to chemoresistance in acute myeloid leukemia (AML). Downregulation of CDKN2A is associated with inferior overall survival in AML patients and occurs at relapse. Therapeutic targeting of the G(1)S cell cycle restriction point and promotion of apoptosis can enhance chemotherapy response in AML.
Article
Immunology
Melanie Heinlein, Luke C. Gandolfo, Kelin Zhao, Charis E. Teh, Nghi Nguyen, Jonathan B. Baell, Yael Goldfarb, Jakub Abramson, Johannes Wichmann, Anne K. Voss, Andreas Strasser, Gordon K. Smyth, Tim Thomas, Daniel H. D. Gray
Summary: The histone acetyltransferase KAT7 plays a critical role in promoting transcription of peripheral tissue genes and regulating immunological tolerance in thymic epithelial cells. Deficiency of KAT7 leads to impaired immunological tolerance and the development of autoimmune diseases.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Susanne Mueller, Suzanne Ackloo, Arij Al Chawaf, Bissan Al-Lazikani, Albert Antolin, Jonathan B. Baell, Hartmut Beck, Shaunna Beedie, Ulrich A. K. Betz, Gustavo Arruda Bezerra, Paul E. Brennan, David Brown, Peter J. Brown, Alex N. Bullock, Adrian J. Carter, Apirat Chaikuad, Mathilde Chaineau, Alessio Ciulli, Ian Collins, Jan Dreher, David Drewry, Kristina Edfeldt, Aled M. Edwards, Ursula Egner, Stephen Frye, Stephen M. Fuchs, Matthew D. Hall, Ingo Hartung, Alexander Hillisch, Stephen H. Hitchcock, Evert Homan, Natarajan Kannan, James R. Kiefer, Stefan Knapp, Milka Kostic, Stefan Kubicek, Andrew R. Leach, Sven Lindemann, Brian D. Marsden, Hisanori Matsui, Jordan L. Meier, Daniel Merk, Maurice Michel, Maxwell R. Morgan, Anke Mueller-Fahrnow, Dafydd R. Owen, Benjamin G. Perry, Saul H. Rosenberg, Kumar Singh Saikatendu, Matthieu Schapira, Cora Scholten, Sujata Sharma, Anton Simeonov, Michael Sundstrom, Giulio Superti-Furga, Matthew H. Todd, Claudia Tredup, Masoud Vedadi, Frank von Delft, Timothy M. Willson, Georg E. Winter, Paul Workman, Cheryl H. Arrowsmith
Summary: Twenty years after the first draft of the human genome was published, our understanding of the human proteome is still incomplete. The majority of proteins in the human proteome remain uncharacterized, with only a small percentage successfully targeted for drug discovery. Target 2035 aims to bridge this gap by developing new technologies for the entire human proteome by 2035.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lisa Barbaro, Gayathri Nagalingam, James A. Triccas, Lendl Tan, Nicholas P. West, Jonathan B. Baell, Daniel L. Priebbenow
Summary: Despite safety concerns, the clinical use of bedaquiline has been limited, prompting research into modifications within the quinoline ring to discover new variants with improved safety profiles. The development of novel synthetic strategies led to the discovery that anti-tubercular activity could be maintained following replacement of the quinoline motif with pyridine heterocycles, potentially opening up new avenues for improved anti-tubercular therapeutics.
RSC MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Jayme L. Dahlin, Douglas S. Auld, Ina Rothenaigner, Steve Haney, Jonathan Z. Sexton, J. Willem M. Nissink, Jarrod Walsh, Jonathan A. Lee, John M. Strelow, Francis S. Willard, Lori Ferrins, Jonathan B. Baell, Michael A. Walters, Bruce K. Hua, Kamyar Hadian, Bridget K. Wagner
Summary: Nuisance compounds, which can waste resources and erode scientific trust, are a major obstacle in realizing the full potential of chemical biology. Understanding and addressing these compounds in complex cell-based assays is essential for efficient drug discovery and research.
CELL CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jonathan B. Baell
Summary: The public-private interface in drug discovery is a dynamic stage that allows for higher risk but more rewarding research. Adequate resourcing is a perpetual challenge, but persistence, optimism, and flexibility can lead to a highly rewarding career. Selected examples in this account support this notion.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2021)
