Human induced pluripotent stem cells (hiPSCs) have transformed conventional drug discovery pathways in recent years. In particular, recent advances in hiPSC biology, including organoid technologies, have highlighted a new potential for neural drug discovery with clear advantages over the use of primary tissues. This is important considering the financial and social burden of neurological health care worldwide, directly impacting the life expectancy of many populations. Patient-derived iPSCs-neurons are invaluable tools for novel drug-screening and precision medicine approaches directly aimed at reducing the burden imposed by the increasing prevalence of neurological disorders in an aging population. 3-Dimensional self-assembled or so-called 'organoid' hiPSCs cultures offer key advantages over traditional 2D ones and may well be gamechangers in the drug-discovery quest for neurological disorders in the coming years.
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http://dx.doi.org/10.3390/molecules25051150 | DOI Listing |
World J Microbiol Biotechnol
January 2025
Department of Environmental Engineering, Kyungpook National University, 80 Daehak-Ro, Buk-Gu, Daegu, 41566, South Korea.
Endophytes have significant prospects for applications beyond their existing utilization in agriculture and the natural sciences. They form an endosymbiotic relationship with plants by colonizing the root tissues without detrimental effects. These endophytes comprise several microorganisms, including bacteria and fungi.
View Article and Find Full Text PDFActa Pharmacol Sin
January 2025
Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
Computational target identification plays a pivotal role in the drug development process. With the significant advancements of deep learning methods for protein structure prediction, the structural coverage of human proteome has increased substantially. This progress inspired the development of the first genome-wide small molecule targets scanning method.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications.
View Article and Find Full Text PDFChem Asian J
January 2025
Chiang Mai University, Chemistry, 239 Huay Kaew Road, Muang District, 50200, Chiang Mai, THAILAND.
The Ph3P-I2-mediated reactions between isatins and amines were extensively investigated leading to the discovery of highly selective and divergent routes toward the synthesis of two distinct classes of indole-based frameworks. Through a strategic design of the reaction paths, we overcome potential side reactions to achieve convenient and straightforward one-pot methods to access either indoloquinazolines with C-12 carboxamide or 2-aminosubstituted indol-3-ones using the same reagent system. Mechanistic studies reveal the role of Ph3P-I2 in governing product selectivity, providing an efficient route to novel fused-indolone derivatives with promising applications in drug discovery and medicinal chemistry.
View Article and Find Full Text PDFBMJ Glob Health
January 2025
Sickle Cell Programme, Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Despite progress in healthcare services for individuals living with sickle cell disease (SCD) in Africa, substantial gaps remain in advanced treatments for SCD. To help address this burden, Tanzania has established one of the largest single-centre SCD programmes in the world and developed an advanced therapy programme for SCD focused on patient engagement and advocacy, clinical activities involving exchange blood transfusion (ExBT) and haematopoietic stem cell transplant (HSCT), gene therapy (GT) preparedness, and enabling partnerships. This report describes the programme's genesis, structure and progress achieved.
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