Article
Chemistry, Medicinal
Giuseppe Faudone, Rezart Zhubi, Fatih Celik, Stefan Knapp, Apirat Chaikuad, Jan Heering, Daniel Merk
Summary: TLX is a master regulator of neurogenesis and acts as a transcriptional repressor of tumor suppressor genes to maintain neuronal stem cell homeostasis. The development of a potent TLX agonist, with submicromolar potency and high selectivity, has been reported, providing a valuable tool for functional studies on TLX.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Camille Barbier, Ali Mansour, Aiten Ismailova, Fatemeh Sarmadi, David A. Scarlata, Manuella Bouttier, Camille Zeitouni, Catherine Wang, James L. Gleason, John H. White
Summary: This study developed a new type of bifunctional molecules that combine vitamin D receptor agonists with histone deacetylase inhibitors, showing anti-tumor effects in treating triple-negative breast cancer. The solubility of these molecules was improved by introducing nitrogen. Gene expression profiling studies revealed that these molecules have similar mechanisms of action to vitamin D, and regulate genes related to immune cell infiltration into tumors, as well as suppressing the expression of molecules promoting breast cancer growth and metastasis.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Claudia Theys, Dorien Lauwers, Claudina Perez-Novo, Wim Vanden Berghe
Summary: Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic and the most common cause of chronic liver disease worldwide. This review focuses on the epigenetic regulation of NAFLD, particularly the role of the nuclear receptor PPAR alpha in lipid metabolism. The interaction between PPAR alpha and epigenetic enzymes has become a potential therapeutic target for NAFLD.
Article
Chemistry, Medicinal
Yongtao Li, Wenwei Lin, Sergio C. Chai, Jing Wu, Kavya Annu, Taosheng Chen
Summary: In this study, a selective and potent PXR antagonist was discovered through structural optimization of a series of compounds. This finding provides novel PXR inhibitors for basic research and future clinical studies and sheds light on reducing compound's binding affinity to PXR.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Sergio Hidalgo-Figueroa, Ana Rodriguez-Luevano, Julio C. Almanza-Perez, Abraham Giacoman-Martinez, Rolffy Ortiz-Andrade, Ismael Leon-Rivera, Gabriel Navarrete-Vazquez
Summary: The manuscript describes the design of two molecules targeting PPAR gamma and GPR40 receptors, with compound 1 showing strong activity in increasing mRNA expression levels of PPAR gamma, GLUT4, and GPR40. Additionally, compound 1 exhibited a moderate increase in insulin secretion and calcium mobilization. These findings suggest that compound 1 acts as a dual PPAR gamma and GPR40 agonist, offering better glycemic control than current treatments.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kiran Bharat Lokhande, Sangeeta Ballav, Rohit Singh Yadav, K. Venkateswara Swamy, Soumya Basu
Summary: Through molecular docking and dynamic simulation, derivatives of Kaempferol, Quercetin, and Resveratrol were found to have high binding affinities with PPAR-gamma, indicating their potential as anti-inflammatory and anti-cancer agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Yukiko Yamashita, Keigo Gohda, Yusuke Iguchi, Ko Fujimori, Keisuke Oda, Arisa Masuda, Mizuho Une, Naoki Teno
Summary: This study identified a benzimidazole compound 18 with dual partial agonistic activity for FXR and PPAR gamma, which could be a novel candidate for treating NAFLD associated with type 2 diabetes mellitus.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Youbo Zhang, Tingting Yan, Tianxia Wang, Xiaoyan Liu, Keisuke Hamada, Dongxue Sun, Yizheng Sun, Yanfang Yang, Jing Wang, Shogo Takahashi, Qiong Wang, Kristopher W. Krausz, Changtao Jiang, Cen Xie, Xiuwei Yang, Frank J. Gonzalez
Summary: The study uncovers a metabolic crosstalk between PPAR alpha and CYP2E1, showing that deficiency of CYP2E1 promotes adipose tissue browning and increases energy expenditure through the activation of PPAR alpha.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Cell Biology
Wenxiang Hu, Chunjie Jiang, Mindy Kim, Yang Xiao, Hannah J. Richter, Dongyin Guan, Kun Zhu, Brianna M. Krusen, Arielle N. Roberts, Jessica Miller, David J. Steger, Mitchell A. Lazar
Summary: This study provides insights into the specific metabolic functions of PPAR gamma isoforms, suggesting that they can be targeted for improving therapy for insulin resistance and diabetes.
GENES & DEVELOPMENT
(2022)
Article
Biology
Caleb R. Glassman, Leon Su, Sonia S. Majri-Morrison, Hauke Winkelmann, Fei Mo, Peng Li, Magdiel Perez-Cruz, Peggy P. Ho, Ievgen Koliesnik, Nadine Nagy, Tereza Hnizdilova, Lora K. Picton, Marek Kovar, Paul Bollyky, Lawrence Steinman, Everett Meyer, Jacob Piehler, Warren J. Leonard, K. Christopher Garcia
Summary: Interleukin-2 (IL-2) is a pleiotropic cytokine that mediates both pro- and anti-inflammatory functions, with different sensitivities in immune cells due to cell type and activation state-dependent expression of receptors and signaling pathway components. Using structure-based design, IL-2 variants were created to titrate maximum signal strength across cell types, leading to cell type-dependent differences in gene expression. IL-2 partial agonists can be used to calibrate intrinsic differences in response thresholds across responding cell types to narrow pleiotropic actions.
Article
Chemistry, Medicinal
Susheel J. Nara, Srinivas Jogi, Srinivas Cheruku, Sarkunam Kandhasamy, Firoz Jaipuri, Pavan Kalyan Kathi, Subba Reddy, Sanket Sarodaya, Erica M. Cook, Tao Wang, Doree Sitkoff, Karen A. Rossi, Max Ruzanov, Susan E. Kiefer, Javed A. Khan, Mian Gao, Satyanarayana Reddy, Sankara L. V. J. Sivaprasad, Ramola Sane, Kathy Mosure, Xiaoliang Zhuo, Gary G. Cao, Milinda Ziegler, Anthony Azzara, John Krupinski, Matthew G. Soars, Bruce A. Ellsworth, Dean A. Wacker
Summary: This study reports the discovery and preclinical evaluation of compound 32, a nonbile acid farnesoid X receptor (FXR) agonist, which exhibits tissue-selective effects in vivo. Additionally, this study demonstrates differential induction of Fgf15 in the liver and ileum by FXR agonists. Compound 32 shows robust antifibrotic efficacy, presenting an opportunity for reduced adverse effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Thermodynamics
Qirui Guo, Weizhong Shi, Hongkun Zhao, Wanxin Li, Ali Farajtabar
Summary: This study investigated the thermodynamic equilibrium solubility of thiamphenicol in different solvent compositions, as well as the solvation behavior of the compound. A quantitative study of the molecular surface and Hirshfeld surface analysis were used to explain the electrostatic properties of thiamphenicol. Various models were utilized to correlate the solubility data, and positive solvation values indicated that acetone/acetonitrile preferentially solvate thiamphenicol.
JOURNAL OF CHEMICAL THERMODYNAMICS
(2023)
Article
Thermodynamics
Renata Cazelato Gaioto, Mariana Carolina Gipiela Correa Dias, Papa Matar Ndiaye, Luciana Igarashi-Mafra, Marcos R. Mafra
Summary: In this study, experimental data on choline chloride aqueous solutions were analyzed in terms of solubility, density, speed of sound, and dynamic viscosity. From these data, thermodynamic properties and intermolecular interactions were evaluated, providing insights into the solution behavior. Surface tension data were also determined to understand the behavior of this organic compound. The results suggest significant ionic interactions and changes in ion hydration with increasing concentration, and reveal the surfactant-like behavior of the salt.
FLUID PHASE EQUILIBRIA
(2023)
Article
Biochemistry & Molecular Biology
Ryota Shizu, Yuta Otsuka, Chizuru Ishii, Kanako Ezaki, Kouichi Yoshinari
Summary: The nuclear receptor PPAR alpha controls fatty acid metabolism and can be inhibited by the xenobiotic receptor CAR, preventing lipid metabolism. Activation of PPAR alpha increases gene expression related to fatty acid metabolism. PPAR alpha binds to the promoter region of the CAR gene and induces its activity. CAR functions as a negative feedback factor for PPAR alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Boxuan Lou, Yue Xu, Xiaolan Qin, Chang Liu, Shujun Wang, Haikuan Yuan, Xijian Liu, Lijuan Zhang, Jie Lu
Summary: In this study, the solubility of unsolvated crystalline (R)-equol and solvated crystalline (R)-equol in various solvents were measured and analyzed. It was found that the solubility of unsolvated crystalline (R)-equol was influenced by temperature and the mass fraction of alcohol, and followed a specific solubility order. The transformation temperatures between unsolvated and solvated forms were determined. The experimental solubility data were correlated using different equations, with the modified Apelblat equation performing the best. Molecular simulation was conducted to explain the experimental phenomena.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Chemistry, Medicinal
Sayaka Nomura, Kaori Endo-Umeda, Shinya Fujii, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Shusuke Tomoshige, Sayaka Nomura, Kenji Ohgane, Yuichi Hashimoto, Minoru Ishikawa
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Biochemistry & Molecular Biology
Yuko Nishiyama, Shinya Fujii, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Biochemistry & Molecular Biology
Hiroko Yamashita, Shusuke Tomoshige, Sayaka Nomura, Kenji Ohgane, Yuichi Hashimoto, Minoru Ishikawa
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Review
Chemistry, Multidisciplinary
Shusuke Tomoshige, Minoru Ishikawa
Summary: Neurodegenerative disorders are a group of diseases that cause neural cell damage, resulting in motility and cognitive dysfunctions. Innovative technologies for chemical protein degradation offer a potential solution for eliminating target proteins that traditional drugs cannot treat.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Medicinal
Minoru Ishikawa, Shusuke Tomoshige, Yosuke Demizu, Mikihiko Naito
Editorial Material
Chemistry, Medicinal
Shaomeng Wang, Gunda Georg, Minoru Ishikawa, Tomohiko Ohwada, Satoshi Shuto, Takayoshi Suzuki
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Ryuta Shioi, Fumika Karaki, Hiromasa Yoshioka, Tomomi Noguchi-Yachide, Minoru Ishikawa, Kosuke Dodo, Yuichi Hashimoto, Mikiko Sodeoka, Kenji Ohgane
Review
Biochemistry & Molecular Biology
Shusuke Tomoshige, Minoru Ishikawa
Summary: PROTACs, as bifunctional molecules, have shown poor bioavailability due to their high molecular weight, but recent developments focusing on in vivo synthesis and using PROTACs as chemical tools have significant implications for drug discovery.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Keita Nakane, Shinichi Sato, Tatsuya Niwa, Michihiko Tsushima, Shusuke Tomoshige, Hideki Taguchi, Minoru Ishikawa, Hiroyuki Nakamura
Summary: A new strategy for histidine functionalization using an umpolung approach under singlet oxygen generation conditions was reported. This rapid labeling method could be applied for instant protein labeling and proximity labeling on the nanometer scale using the short diffusion distance of singlet oxygen.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Satsuki Obara, Keita Nakane, Chizu Fujimura, Shusuke Tomoshige, Minoru Ishikawa, Shinichi Sato
Summary: This study developed a tyrosine-selective modification method for HSA, with laccase-catalyzed method being able to efficiently introduce functional groups under mild conditions. Mass spectrometry analysis identified Y84, Y138, and Y401 as the main modification sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Junki Morimoto, Kazunori Miyamoto, Yuki Ichikawa, Masanobu Uchiyama, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
Summary: Converting the symmetrical molecular structure of drug candidates into asymmetrical form enhances aqueous solubility, even with increased hydrophobicity. This strategy can improve membrane permeability and biological activity.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Physical
Keita Nakane, Tatsuya Niwa, Michihiko Tsushima, Shusuke Tomoshige, Hideki Taguchi, Hiroyuki Nakamura, Minoru Ishikawa, Shinichi Sato
Summary: The novel function of BODIPY as a catalyst for chemical labelling of histidine is revealed. It oxidizes histidine residues using singlet oxygen produced by its photosensitizer property, and the oxidized histidine is then trapped by a nucleophile. This selective labelling allows site-selective functionalization of proteins/peptides.
Article
Biochemistry & Molecular Biology
Keita Nakane, Haruto Nagasawa, Chizu Fujimura, Eri Koyanagi, Shusuke Tomoshige, Minoru Ishikawa, Shinichi Sato
Summary: This article introduces a proximity labeling technique for studying protein-protein interactions. The technique uses photocatalytic reactions to label proteins, and it was found that various dye molecules can serve as catalysts. Furthermore, catalysts that selectively modify specific amino acid residues were identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Organic
Yuki Ichikawa, Michiaki Hiramatsu, Yusuke Mita, Makoto Makishima, Yotaro Matsumoto, Yui Masumoto, Atsuya Muranaka, Masanobu Uchiyama, Yuichi Hashimoto, Minoru Ishikawa
Summary: The study found that meta-isomers with non-flat substituents tend to have the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers of disubstituted benzenes. The introduction of a non-flat substituent at the meta position of a benzene substructure may be a promising approach for improving the aqueous solubility of drug candidates.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)