Review
Chemistry, Medicinal
Hairong Tang, Ao Zhang
Summary: Although monkeypox has been endemic in Africa for 50 years, it has not received enough attention to prevent it from becoming an epidemic. From January 2022 to January 2023, over 84,000 cases were reported worldwide, making monkeypox a growing global health threat. This review discusses the biology, epidemiology, and new therapeutic options for monkeypox, as well as potential inhibitors and future directions in this field.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Kosuke Fukui, Kazushi Arai, Yuka Tanaka, Yuki Aoi, Vandna Kukshal, Joseph M. Jez, Martin F. Kubes, Richard Napier, Yunde Zhao, Hiroyuki Kasahara, Ken-ichiro Hayashi
Summary: The phytohormone auxin, indole-3-acetic acid (IAA), plays a significant role in plant development. The research characterizes a potent GH3 inhibitor called kakeimide that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown experiments demonstrate that auxin turnover is rapid, suggesting that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Hadar Grimberg, Vinay S. Tiwari, Benjamin Tam, Lihi Gur-Arie, Daniela Gingold, Lea Polachek, Barak Akabayov
Summary: In this study, data-driven algorithms were employed to identify phenylthiazole-containing molecules that can bind to the RNA hairpin of Mycobacterium tuberculosis. Functional validation of computationally selected molecules resulted in the discovery of potent inhibitors targeting the ribosomal peptidyl transferase center.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Chemistry, Medicinal
Robert D. Barrows, Daniel E. Jeffries, Mahesh Vishe, Hanna Tukachinsky, Shao-Liang Zheng, Fanfan Li, Zhenjie Ma, Xiaolei Li, Shujuan Jin, Haobin Song, Ruonan Zhang, Shaofeng Zhang, Jing Ni, Haofei Luan, Lei Wen, Yan Rongshan, Chen Ying, Matthew D. Shair
Summary: Recent studies have shown that NNMT upregulation is necessary for maintaining the phenotype of cancer-associated fibroblasts, making NNMT a potential therapeutic target in cancer. Despite the discovery of several small-molecule inhibitors, there is still a need for more potent and selective drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Zhen Wang, Jiafu Ying, Xuanpu Zhang, Chen Miao, Yu Xiao, Jie Zou, Baoen Chen
Summary: Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, and thus lipid-modifying enzymes and substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has greatly influenced our understanding of lipid-modification biology and potential therapeutics. In this review, recent progress in small-molecule targeting of protein lipidation is summarized and therapeutic opportunities are highlighted.
Review
Biochemistry & Molecular Biology
Fan Yang, Zhigang Hu, Zhigang Guo
Summary: DNA damage repair is crucial for maintaining genomic stability and integrity, and FEN1 plays a critical role in this process. Abnormal expression or mutation of FEN1 is associated with various diseases, including cancers, making it a therapeutic target for cancer treatment. Small-molecule compounds targeting FEN1 have been developed and show promise in cancer therapy.
Review
Biochemistry & Molecular Biology
Kearsley M. Dillon, John B. Matson
Summary: Persulfides have emerged as reactive sulfur species with enhanced antioxidant abilities compared to hydrogen sulfide, but their instability and cross-reactivity hinder the elucidation of their precise biological roles. To facilitate the study of persulfides, chemists have designed various chemical tools and techniques, including persulfide trapping reagents and sensors, as well as persulfide donors that release persulfides in response to triggers.
ACS CHEMICAL BIOLOGY
(2021)
Editorial Material
Plant Sciences
Ralf Welsch, Alisher Touraev, Klaus Palme
Summary: The fertilized egg is the starting point for multicellular organism development, plant cells have the ability to regenerate, and the fate of regenerating tissues is regulated by plant hormones.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Biochemistry & Molecular Biology
Vasily A. Shenshin, Camille Lescanne, Guillaume Gines, Yannick Rondelez
Summary: This paper introduces a general strategy to interface DNA-based circuits with non-DNA signals through input-translating modules, allowing the construction of sensing circuits with good specificity and sensitivity. The programmability of the DNA layer enables signal processing operations such as logical inversion, signal modulation, and classification tasks.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Agronomy
Danica Goggin, Candy Taylor, Roberto Busi, Chad Sayer, Andrew Wells, Mark Slatter, Ken Flower
Summary: Resistance to synthetic auxin herbicides, including 2,4-D, has become a major problem in dicotyledonous weeds worldwide. While some compounds showed mild synergism with 2,4-D, the response was not consistent enough for further study. Therefore, nonchemical control techniques and alternative herbicide modes of action should be employed to delay the development of resistance.
Review
Medicine, General & Internal
Jianjing Lin, Shicheng Jia, Weifei Zhang, Mengyuan Nian, Peng Liu, Li Yang, Jianwei Zuo, Wei Li, Hui Zeng, Xintao Zhang
Summary: Osteoarthritis is a degenerative disease characterized by joint pain, caused by factors such as fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments only delay its progression, while small molecule inhibitors targeting proteins show promising effects in managing osteoarthritis. This review examines small molecule inhibitors targeting various proteins and discusses disease-modifying osteoarthritis drugs based on them, providing valuable insights for the treatment of osteoarthritis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Fatemeh Emadi, Jimma Lenjisa, Laychiluh Mekonnen, Shudong Wang
Summary: As the fifth pillar of cancer treatment, immunotherapy has revolutionized therapeutic strategies by focusing on the host's immune system. The discovery of immune-modulatory effects for kinase inhibitors has opened up new possibilities in this approach, as these small molecule inhibitors not only directly target essential proteins for tumor survival and proliferation, but also stimulate immune responses against malignant cells.
DRUG DISCOVERY TODAY
(2023)
Review
Pharmacology & Pharmacy
Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Summary: Immunotherapy has revolutionized cancer treatment, with current therapies mostly based on antibodies. However, these therapies have limitations in terms of pharmacokinetics and immunogenicity. To overcome these limitations, researchers have focused on developing small molecule-based immunotherapy. This review provides an overview of the progress in small molecule-based immunomodulators for cancer therapy, including targeting PD-1/PD-L1, chemokine receptors, STING, TLR, etc. The importance of combining small molecule-based immunomodulators with therapeutic antibodies is also highlighted.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Biotechnology & Applied Microbiology
Namita Khajanchi, Krishanu Saha
Summary: Biomedical research has been revolutionized by CRISPR-Cas systems, but there are still challenges in terms of editing efficiency and safety. Recent studies have made progress in controlling the expression and activity of Cas systems, including the use of small molecules as regulatory switches, which have the potential to improve the efficiency of in vivo genome editing and reduce adverse effects.
Review
Biochemistry & Molecular Biology
Chao Zhang, Qian Xie, Chi Cheong Wan, Zhe Jin, Chun Hu
Summary: HIV-1 integrase plays a crucial role in HIV-1 treatment, but issues like drug resistance require further research. This review discussed the structure, function, and recent advances in small-molecule inhibitors of HIV-1 integrase.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yuki Aoi, Akira Oikawa, Ryosuke Sasaki, Jirong Huang, Ken-ichiro Hayashi, Hiroyuki Kasahara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Plant Sciences
Yuki Aoi, Keita Tanaka, Sam David Cook, Ken-Ichiro Hayashi, Hiroyuki Kasahara
PLANT AND CELL PHYSIOLOGY
(2020)
Article
Plant Sciences
Imari Koike, Sachi Watanabe, Karin Okazaki, Ken-ichiro Hayashi, Hiroyuki Kasahara, Koichiro Shimomura, Mikihisa Umehara
Article
Biochemistry & Molecular Biology
Eiko Takubo, Makoto Kobayashi, Shoko Hirai, Yuki Aoi, Chennan Ge, Xinhua Dai, Kosuke Fukui, Ken-ichiro Hayashi, Yunde Zhao, Hiroyuki Kasahara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Plant Sciences
Jun Takeuchi, Kosuke Fukui, Yoshiya Seto, Yousuke Takaoka, Masanori Okamoto
Summary: Small-molecule plant hormones play a crucial role in controlling plant growth, development, differentiation, and environmental responses. Through genomic decoding of model plants with genetic mutants, scientists have elucidated the molecular mechanisms of nine types of plant hormones and identified the structure of hormone receptors. Studies on the three-dimensional structure of ligand-receptor complexes have revealed the details of ligand perception mechanisms.
Article
Cell Biology
Ken-Ichiro Hayashi
Summary: Recent molecular genetic and structural studies have provided insights into the regulatory pathways of plant hormones, expanding the application of chemical biology methods in auxin research. Small-molecule modulators generated based on studies of auxin regulatory pathways are now widely used in dissecting auxin biology in diverse plants.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2021)
Article
Plant Sciences
Cuiling Li, Guangchao Liu, Xiaoyu Geng, Chunmei He, Taiyong Quan, Ken-Ichiro Hayashi, Ive De Smet, Helene S. Robert, Zhaojun Ding, Zhong-Bao Yang
Summary: The study revealed that PIN and AUX1/LAX proteins were up-regulated in the root-apex transition zone in response to aluminum stress, coordinating the local auxin accumulation and root growth inhibition in that region. Moreover, the up-regulation of PIN1 under aluminum stress was co-regulated by ethylene and auxin.
Article
Multidisciplinary Sciences
Ken-ichiro Hayashi, Kazushi Arai, Yuki Aoi, Yuka Tanaka, Hayao Hira, Ruipan Guo, Yun Hu, Chennan Ge, Yunde Zhao, Hiroyuki Kasahara, Kosuke Fukui
Summary: Auxin inactivation is crucial for plant development, with the main pathway in Arabidopsis involving conjugation by GH3 IAA-amidosynthetases, oxidation by DAO1 dioxygenase, and hydrolysis by ILR1. These steps illustrate the significance of auxin homeostasis in plant development.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Xiang Huang, Jan Maisch, Ken-Ichiro Hayashi, Peter Nick
Summary: The complexity of auxin signaling is due to multiple auxin receptors, which trigger differential signaling. Fluorescent auxin analogs were used to study the subcellular localization of auxin-binding sites. The results show that different analogs bind to different subcellular compartments, indicating the differential signaling in response to these artificial auxins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kosuke Fukui, Kazushi Arai, Yuka Tanaka, Yuki Aoi, Vandna Kukshal, Joseph M. Jez, Martin F. Kubes, Richard Napier, Yunde Zhao, Hiroyuki Kasahara, Ken-ichiro Hayashi
Summary: The phytohormone auxin, indole-3-acetic acid (IAA), plays a significant role in plant development. The research characterizes a potent GH3 inhibitor called kakeimide that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown experiments demonstrate that auxin turnover is rapid, suggesting that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Plant Sciences
Qing Wang, Hugues De Gernier, Xingliang Duan, Yuanming Xie, Danny Geelen, Ken-ishiro Hayashi, Wei Xuan, Markus Geisler, Kirsten ten Tusscher, Tom Beeckman, Steffen Vanneste
Summary: LR positioning and development are regulated by auxin production, transport, and inactivation. This study demonstrates the impact of GH3-type auxin conjugating enzymes and DAO1 in LR development. The gh3hex mutants exhibit increased LR density due to enhanced initiation and faster progression, with GH3 activities controlling LR formation. GH3-mediated auxin inactivation attenuates LR development by modulating meristem activities and apical meristem size, resulting in accelerated auxin response oscillations and increased LR initiation rates.
Article
Multidisciplinary Sciences
Aisha Yesbolatova, Yuichiro Saito, Naomi Kitamoto, Hatsune Makino-Itou, Rieko Ajima, Risako Nakano, Hirofumi Nakaoka, Kosuke Fukui, Kanae Gamo, Yusuke Tominari, Haruki Takeuchi, Yumiko Saga, Ken-ichiro Hayashi, Masato T. Kanemaki
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Yuki Aoi, Hayao Hira, Yuya Hayakawa, Hongquan Liu, Kosuke Fukui, Xinhua Dai, Keita Tanaka, Ken-ichiro Hayashi, Yunde Zhao, Hiroyuki Kasahara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
