In this paper we describe Zeneth, a new expert computational system for the prediction of forced degradation pathways of organic compounds. Intermolecular reactions such as dimerization, reactions between the query compound and its degradants, as well as interactions with excipients can be predicted. The program employs a knowledge base of patterns and reasoning rules to suggest the most likely transformations under various environmental conditions relevant to the pharmaceutical industry. Building the knowledge base is facilitated by data sharing between the users.
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http://dx.doi.org/10.1021/mp400083h | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Background/objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn's disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions.
Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines.
Int J Mol Sci
January 2025
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Protocadherin-7 (Pcdh7) is a member of the non-clustered protocadherin δ1 subgroup within the cadherin superfamily. Pcdh7 has been shown to control osteoclast differentiation via the protein phosphatase 2A (PP2A)-glycogen synthase kinase-3β (GSK3β)-small GTPase signaling axis. As protocadherins serve multiple biological functions, a deeper understanding of Pcdh7's biological features is valuable.
View Article and Find Full Text PDFBiomolecules
January 2025
Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede Bionorte, Universidade Federal do Pará, Belém 66075-110, PA, Brazil.
Aromatic plants are rich sources of essential oils (EOs), recognized for their therapeutic properties due to their diversity of phytochemicals. This study investigated the anxiolytic and antidepressant effects of essential oil (MsEO) through inhalation in an animal model and its in vitro anticholinesterase (AChE) activity. The EO was obtained by hydrodistillation, and its volatile constituents were analyzed by GC-MS.
View Article and Find Full Text PDFBiomolecules
January 2025
Research and Education Resource Center, Peoples Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
Post-translational modifications of proteins via palmitoylation, a thioester linkage of a 16-carbon fatty acid to a cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing their function. Little is known about how altered palmitoylation affects function at the systemic level and contributes to CNS pathology. However, recent studies suggested a role for the downregulation of palmitoyl acetyltransferase (DHHC) 21 gene expression in the development of Major Depressive Disorder (MDD)-like syndrome.
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