Article
Chemistry, Medicinal
Timothy B. Dunn, Gustavo M. Seabra, Taewon David Kim, K. Euridice Juarez-Mercado, Chenglong Li, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: The quantification of chemical diversity has extensive applications across various fields. With the expansion of chemical libraries, it is crucial to develop efficient methods for quantifying and visualizing the diversity of large-scale chemical libraries. This article introduces a new extended similarity indices method to measure the fingerprint-based diversity of chemical libraries and proposes the Chemical Library Networks (CLNs) framework for visually representing the chemical space of large libraries.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Marion Sisquellas, Marco Cecchini
Summary: PrepFlow is a toolkit for chemical library preparation and management, which efficiently processes compound lists and outputs 3D molecular structures. The tool excels in execution speed, HPC resource utilization, and archiving strategy, significantly improving the efficiency of drug discovery projects.
MOLECULAR INFORMATICS
(2021)
Review
Chemistry, Medicinal
Nitesh Mani Tripathi, Anupam Bandyopadhyay
Summary: High-throughput virtual screening (HTVS) is an important biopharmaceutical technology that utilizes computational algorithms to discover biologically active compounds from large compound libraries, saving resources and time in drug discovery. Peptide-based drug discovery has gained momentum in recent years, highlighting the need for a high-fidelity HTVS platform for chemically versatile peptide libraries.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kirill V. Sukhoverkov, Maxime G. Corral, Julie Leroux, Joel Haywood, Philipp Johnen, Trevor Newton, Keith A. Stubbs, Joshua S. Mylne
Summary: By exploiting the evolutionary relationship between Plasmodium falciparum and plants, a novel herbicide compound, MMV1206386, with potency comparable to commercial herbicides and a new mode of action was discovered. Weighted rules were shown to be effective in herbicide discovery programs.
Review
Biochemical Research Methods
Louison Fresnais, Pedro J. Ballester
Summary: Increasing the size of training datasets improves the accuracy of machine learning-based scoring functions in structure-based virtual screening, and using massive test sets can lead to fast discovery of drug leads with low-nanomolar potency. Screening larger compound libraries results in the identification of more potent actives, and ranking molecules with more accurate machine learning-based scoring functions can further enhance their potency. Additionally, classical and machine learning-based scoring functions often find different actives, suggesting the benefit of using both types of scoring functions on multiple targets.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Biochemical Research Methods
Natesh Singh, Ludovic Chaput, Bruno O. Villoutreix
Summary: The interaction between life sciences and advancing technology leads to continuous growth of chemical data, with virtual screening methods being popular in pharmaceutical research. Web-based tools assist scientists in conducting virtual screening experiments, contributing to the design of bioactive molecules and drug development teaching.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Chemistry, Medicinal
Ram K. Modukuri, Diana Monsivais, Feng Li, Murugesan Palaniappan, Kurt M. Bohren, Zhi Tan, Angela F. Ku, Yong Wang, Chandrashekhar Madasu, Jian-Yuan Li, Suni Tang, Gabriella Miklossy, Stephen S. Palmer, Damian W. Young, Martin M. Matzuk
Summary: Through screening 4.17 billion DNA-encoded chemical library molecules, we identified two selective kinase inhibitors, CDD-1115 and CDD-1431, for BMPR2. Further research led to the development of two more potent inhibitors, CDD-1281 and CDD-1653. This study demonstrates the reliability of DNA-encoded chemistry technology for discovering novel and highly selective kinase inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jeremy S. Disch, Jennifer M. Duffy, Esther C. Y. Lee, Diana Gikunju, Betty Chan, Benjamin Levin, Michael Monteiro, Sarah A. Talcott, Anthony C. Lau, Fei Zhou, Anton Kozhushnyan, Neil E. Westlund, Patrick B. Mullins, Yan Yu, Moritz von Rechenberg, Junyi Zhang, Yelena A. Arnautova, Yanbin Liu, Ying Zhang, Andrew J. McRiner, Anthony D. Keefe, Anna Kohlmann, Matthew A. Clark, John W. Cuozzo, Christelle Huguet, Shilpi Arora
Summary: The research identified novel bispecific degrader leads from DECL screening, with the off-DNA synthesized small molecule exemplar 7 showing nanomolar ER alpha binding, antagonism, and degradation. This approach paves the way for further exploration in developing bispecific degraders of ER alpha with improved efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhaofeng Ye, Fengling Chen, Jiangyang Zeng, Juntao Gao, Michael Q. Zhang
Summary: This study introduces a new method, ScaffComb, which integrates phenotype information and molecular scaffolds for drug combination screening in large-scale databases, resulting in the discovery of novel drug combinations and the identification of new synergistic mechanisms.
Article
Biochemistry & Molecular Biology
Nanxin Liu, Zeyu Yang, Yuying Liu, Xintao Dang, Qingqing Zhang, Jin Wang, Xueying Liu, Jie Zhang, Xiaoyan Pan
Summary: There have been outbreaks of SARS-CoV-2 around the world for over three years, and its variants continue to evolve, posing a major global health threat. A potential inhibitor of the virus's main protease, M-pro, has been identified through virtual screening and biochemical assays.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Esther C. Y. Lee, Andrew J. McRiner, Katy E. Georgiadis, Julie Liu, Zooey Wang, Andrew D. Ferguson, Benjamin Levin, Moritz von Rechenberg, Christopher D. Hupp, Michael Monteiro, Anthony D. Keefe, Allison Olszewski, Charles J. Eyermann, Paolo Centrella, Yanbin Liu, Shilpi Arora, John W. Cuozzo, Ying Zhang, Matthew A. Clark, Christelle Huguet, Anna Kohlmann
Summary: Inhibition of HAO1 is a strategy to reduce toxic oxalate accumulation in PH1 patients. Novel compounds have been identified as potent HAO1 inhibitors, with Compound 5 being optimized to Compound 29 for improved ADME/PK properties. Further research on replacing acidic compounds led to the discovery of a non-acid inhibitor, Compound 31, with weaker potency but increased permeability.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Huiping Yao
Summary: ACE2 is a multifunctional protein that plays a role in both health and disease, serving as a counterregulatory component of RAS function in cardiac protection. It is also relevant to conditions such as ovarian cancer, diabetes, acute lung injury, and fibrotic diseases. Since the outbreak of COVID-19, ACE2 has been recognized as the host receptor for SARS-CoV-2. This study used virtual screening methods to identify potential ACE2 inhibitors and found compounds 154-23-4 and STOCK1N-07141 with potential ACE2 inhibition activities.
Article
Chemistry, Medicinal
Alexandre Bridoux, Shaker A. Mousal
Summary: This study utilized a high technology methodology composed of virtual screening, anticoagulant, and anti-angiogenesis assays to identify potent small-molecule FVIIa inhibitors. The results showed the successful identification of new inhibitors with in vitro effectiveness and anti-angiogenesis properties, suggesting their potential as an effective and safer strategy in coagulation and pathological angiogenesis.
LETTERS IN DRUG DESIGN & DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Gagan Preet, Rishi Vachaspathy Astakala, Jessica Gomez-Banderas, Joy Ebenezer Rajakulendran, Ahlam Haj Hasan, Rainer Ebel, Marcel Jaspars
Summary: Marine biofouling is a major problem for marine vessels and the oil, gas, and renewable energy industries, causing economic losses. The use of natural products, specifically anthraquinones (AQs), as anti-fouling agents shows promise. This study analyzed 2194 compounds from the COCONUT natural products database to identify AQ-related structures with anti-fouling potential. Molecular docking analysis revealed 76 highly docked AQ structures, and structure-based pharmacophore modeling resulted in six unique pharmacophore features.
Article
Chemistry, Medicinal
Regina Pikalyova, Yuliana Zabolotna, Dragos Horvath, Gilles Marcou, Alexandre Varnek
Summary: The development of DNA-encoded library (DEL) technology has brought new challenges to the analysis of chemical libraries. This study introduces the concept of chemical library space (CLS) and compares four representations obtained using generative topographic mapping. These encodings allow for effective comparison of libraries and fine-tuning of matching criteria. The proposed CLS can be used for efficient analysis and selection of chemical libraries.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Cell Biology
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
SCIENCE TRANSLATIONAL MEDICINE
(2017)
Letter
Allergy
Shuichiro Maruoka, Yasuhiro Gon, Kenji Mizumura, Shinichi Okamoto, Kota Tsuya, Sotaro Shikano, Kaori Soda, Isao Naguro, Hidenori Ichijo, Shu Hashimoto
ALLERGOLOGY INTERNATIONAL
(2017)
Article
Biochemistry & Molecular Biology
Ran Cheng, Kohsuke Takeda, Isao Naguro, Tomohisa Hatta, Shun-ichiro Iemura, Tohru Natsume, Hidenori Ichijo, Kazuki Hattori
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2018)
Editorial Material
Cell Biology
Kazuki Hattori, Hidenori Ichijo
Article
Biochemistry & Molecular Biology
Ayane Yamaguchi, Hayate Ishikawa, Mana Furuoka, Masashi Yokozeki, Noriyuki Matsuda, Susumu Tanimura, Kohsuke Takeda
JOURNAL OF BIOCHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Nana Nakada-Motokawa, Taiga Miyazaki, Satoshi Mizuta, Yoshimasa Tanaka, Tatsuro Hirayama, Takahiro Takazono, Tomomi Saijo, Kazuko Yamamoto, Yoshifumi Imamura, Koichi Izumikawa, Katsunori Yanagihara, Koichi Makimura, Kohsuke Takeda, Shigeru Kohno, Hiroshi Mukae
Article
Cell Biology
Shota Nakamura, Ritsuko Masuyama, Kosuke Sakai, Karin Fukuda, Kohsuke Takeda, Susumu Tanimura
Article
Oncology
Makoto Fujimoto, Miki Kamiyama, Kosuke Fuse, Hiroki Ryuno, Takeru Odawara, Natsuki Furukawa, Yasuhiro Yoshimatsu, Tetsuro Watabe, Michaela Prchal-Murphy, Veronika Sexl, Hideaki Tahara, Yoshihiro Hayakawa, Takehiro Sato, Kohsuke Takeda, Isao Naguro, Hidenori Ichijo
Summary: The study demonstrates that ASK1 deficiency promotes NK cell-mediated intravascular tumor cell clearance and upregulates immune response-related genes, including IFN gamma, to enhance the anti-metastatic phenotypes. NK cells are required for these anti-metastatic phenotypes.
Article
Multidisciplinary Sciences
Kengo Watanabe, Kazuhiro Morishita, Xiangyu Zhou, Shigeru Shiizaki, Yasuo Uchiyama, Masato Koike, Isao Naguro, Hidenori Ichijo
Summary: This study reveals that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, leading to its inactivation, while a factor related to poly(ADP-ribose) signaling is identified as an ASK3 inactivation regulator. These findings demonstrate that cells rationally incorporate physicochemical phase separation into their osmosensing systems.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Tianli Zhang, Hiroyasu Tsutsuki, Waliul Islam, Katsuhiko Ono, Kohsuke Takeda, Takaaki Akaike, Tomohiro Sawa
Summary: ATP exposure leads to a sharp decrease in glutathione (GSH) levels in macrophages, triggering NLRP3 inflammasome activation. Exogenous addition of GSH or GSSG can inhibit GSH efflux and attenuate NLRP3 inflammasome activation. This finding may contribute to the development of novel therapeutic strategies for NLRP3 inflammasome-associated disorders.
Article
Biochemistry & Molecular Biology
Toshitaka Nakamura, Motoyuki Ogawa, Kazuki Kojima, Saki Takayanagi, Shunya Ishihara, Kazuki Hattori, Isao Naguro, Hidenori Ichijo
Summary: The study revealed that mitochondrial Ca2+ regulation and hyperpolarization play a key role in lipid peroxidation and ferroptosis under cold stress.
Article
Cell Biology
Carlo De Blasio, Nagendra Verma, Marta Moretti, Samantha Cialfi, Azzurra Zonfrilli, Matteo Franchitto, Federica Truglio, Enrico De Smaele, Hidenori Ichijo, Isao Naguro, Isabella Screpanti, Claudio Talora
Summary: The study investigates the functional interaction between ASK1 and p21 (Waf1/Cip1) in tumorigenesis. It shows that loss of p21 leads to increased keratinocyte proliferation and cell death, while loss of ASK1 reduces apoptosis in p21-deficient keratinocytes. Double knockout of p21 and ASK1 in skin epithelium increases sensitivity to carcinogens, indicating a critical role of p21-dependent ASK1 inactivation in maintaining a balance between cell death, cell-cycle arrest, and successful divisions during stress conditions.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Taiki Baba, Susumu Tanimura, Ayane Yamaguchi, Koichiro Horikawa, Masashi Yokozeki, Saki Hachiya, Shun-Ichiro Iemura, Tohru Natsume, Noriyuki Matsuda, Kohsuke Takeda
Summary: PGAM5 is a protein phosphatase located in the inner mitochondrial membrane, which is cleaved and released into the nucleus upon mitochondrial dysfunction. It interacts with nuclear protein SRm160, dephosphorylates it, and regulates phosphorylation of other SR proteins during mitophagy, potentially coordinating cellular responses to mitochondrial stress at the post-transcriptional and pretranslational levels.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Cell Biology
Takuto Nishida, Isao Naguro, Hidenori Ichijo
Summary: The dynamic balance of NAD(+) through PARP1 consumption and NAMPT synthesis is important in determining the form of cell death under H2O2 stimulation.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Yuki Hayashi, Sho Takatori, Waleed Y. Warsame, Taisuke Tomita, Takao Fujisawa, Hidenori Ichijo
Summary: TOLLIP is a cargo-specific adaptor that selectively clears aberrant ER proteins by coupling them with PI3P-dependent lysosomal trafficking. TOLLIP and ERAD cooperatively safeguard ER proteostasis.
