MEDCHEM NEWS
Online ISSN : 2432-8626
Print ISSN : 2432-8618
ISSN-L : 2432-8618
Search
Advanced search
OR
Browse
Search
Volume 33, Issue 2
Displaying 1-21 of 21 articles from this issue
Show all abstracts
    • |<
    • <
    • 1
    • >
    • >|
  • Innovative Solutions for Drug Discovery in Nissan Chemical
    Norihisa Ishiwata, Tomomichi Chonan
    2023 Volume 33 Issue 2 Pages 54-59
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_54
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    Nissan Chemical Corporation was founded in 1887, which was the first chemical fertilizer manufacturer in Japan. The company was established by Dr. Takamine Jokichi, who has been referred to as the “Father of Modern Biotechnology”, and Eiichi Shibusawa known as the “Father of Japanese Capitalism”. Their pioneering spirit has been inherited in the company as we have continued putting efforts into innovative technologies and promoted greatly transforming our business operations. Here we describe recent progress for the development of innovative drug discovery platform including peptide synthesis technology “SYNCSOL®”, oligonucleotide drug discovery platform and DNA-encoded library technology. We are dedicated to constructing the robust portfolio by expanding the external partnerships based on our business model to achieve “Atelier 2050”, our long-term business plan.
    View full abstract
    Download PDF (971K)
WINDOW
  • Activities of EFPIA
    Takeo Morooka
    2023 Volume 33 Issue 2 Pages 60-63
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_60
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    EFPIA provides the voice of companies committed to researching, developing and bringing new medicines to improve health and quality of life around the world. In order to establish “pharmaceutical industry ecosystem”, EFPIA Japan will strategically work on (1) improving the pharmaceutical R&D and regulatory environment, (2) balancing the sustainability of universal health coverage with the promotion of innovation in the pharmaceutical sector, (3) contributing to the improvement of health literacy, (4) institutional design of cost-effectiveness evaluation that does not hinder access, and (5) utilization of advanced regenerative medicine, gene/cell therapies and digital technology thus contributing to human capacity development.
    View full abstract
    Download PDF (787K)
DISCOVERY
  • Discovery of Soticlestat (TAK-935) , a First-in-class Drug for Antiseizure Medication (ASM)
    Tatsuki Koike, Masato Yoshikawa, Haruhi Ando, Maki Miyamoto, Toshiya N ...
    2023 Volume 33 Issue 2 Pages 64-69
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_64
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    Cholesterol 24-hydroxylase (CH24H, CYP46A1) is a brain-specific CYP enzyme that plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC) . The therapeutic potential of CH24H inhibition had been underexploited partly because of the lack of selective inhibitor reported thus far. In our research to discover CH24H inhibitor based on structure-based drug design (SBDD) , soticlestat was identified as a highly potent CH24H inhibitor with high selectivity over off-target CYPs. Oral administration of soticlestat significantly reduced the seizure frequency in multiple animal models of epilepsy, which led us to develop a CH24H inhibitor for treatment of developmental and epileptic encephalopathies (DEE) . Soticlestat is currently being investigated as a drug for treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) with a novel mechanism of action.
    View full abstract
    Download PDF (1746K)
DISCOVERY
  • Development of oligonucleotide-based PROTACs
    Miyako Naganuma, Nobumichi Ohoka, Yosuke Demizu
    2023 Volume 33 Issue 2 Pages 70-74
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_70
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    Targeted protein degradation using PROTACs is expected to be one of innovative modalities for diseases that are difficult to treat with existing drugs, including cancers. PROTACs mediate the degradation of protein of interest (POIs) by hijacking the activity of E3 ubiquitin ligases for POI ubiquitination and subsequent proteasomal degradation. So far, a number of PROTACs have been developed mainly using small molecules as POI ligands, but it is difficult to adapt them to proteins for which no suitable ligand exists, such as transcription factors (TFs) . Herein, to develop versatile new PROTACs that can target those TFs, oligonucleotide-based PROTACs that utilize a decoy as a ligand binding to the DNA-binding domain of TFs. As proof-of-concept studies, this paper presents details of the design and synthesis of decoy oligonucleotide-based PROTACs using the estrogen receptor a as a model of TFs and the results of various evaluations.
    View full abstract
    Download PDF (2154K)
DISCOVERY
  • Development of Chemical Capping Reaction for Complete Chemical Synthesis of mRNA
    Hiroshi Abe, Kazuya Ogawa, Naoko Abe, Yasuaki Kimura
    2023 Volume 33 Issue 2 Pages 75-78
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_75
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    Recently, mRNA vaccines have been used with great success in SARS-CoV2 infections. However, mRNA vaccines are subject to reduced activity due to the in vivo instability of mRNA and other factors. Therefore, it is effective to introduce chemical modifications to mRNA that are expected to improve its stability, but there is no general synthetic method to achieve this. In this study, we developed a method for complete chemical synthesis of mRNA that avoids the enzymatic method, which is a barrier to the introduction of chemical modifications to mRNA. This method enables the introduction of site-specific chemical modifications to mRNA, and the appropriate chemical modification pattern that maximizes translational activity and stability. This paper describes the development of the complete chemical synthesis method, the structure-activity relationship of chemically modified mRNAs by the complete chemical synthesis method, and the therapeutic effects of mRNA cancer vaccines synthesized by this method.
    View full abstract
    Download PDF (994K)
SEMINAR
  • Tyrosine-/Histidine-selective chemical labeling and photocatalytic control of the labeling reaction
    Shinichi Sato, Keita Nakane
    2023 Volume 33 Issue 2 Pages 79-83
    Published: May 01, 2023
    Released on J-STAGE: May 01, 2023
    DOIhttps://doi.org/10.14894/medchem.33.2_79
    JOURNAL RESTRICTED ACCESS
    Show abstractHide abstract
    Protein chemical modifications targeting natural amino acid residues have contributed significantly to the development of life science. Although approaches targeting nucleophilic amino acid residues have been significantly developed, novel mechanism-based developments are required to extend the range of modifiable amino acid residues and protein modification methods. We have developed modification methods for tyrosine and histidine residues. Tyrosine residues are modified by radical species generated by catalytic oxidation via a single-electron transfer reaction. Histidine residues are modified by oxidation using singlet oxygen and nucleophilic trapping reaction of oxidized histidine intermediate. It was also demonstrated that these reactions could be controlled in proximity to the catalyst, where short-lived, highly reactive chemical species can diffuse.
    View full abstract
    Download PDF (1692K)
BOOKS
Coffee Break
REPORT
    • |<
    • <
    • 1
    • >
    • >|
feedback
 Top