In Vitro to In Vivo Extrapolation of Metabolic Rate Constants for Physiologically Based Pharmacokinetic Models
John C. Lipscomb, Edward V. Ohanian in Toxicokinetics and Risk Assessment, 2016
Living organisms are composed of various small molecules and macro-molecules including proteins, lipids, polysaccharides, and nucleic acids that are termed biomolecules. Biomolecules are organized into three-dimensional structures that make up mammalian cells. Simple biomolecules such as amino acids, sugars, and lipids are the building blocks of macromolecules, which are components of supramolecular complexes such as membranes and ribosomes. Supramolecular complexes are assembled into organelles, which organize into cells (1). Cells are complex integrated entities that combine macromolecular structure and function. Cellular constituents and metabolic pathways are not randomly dispersed in cells, but rather are localized to specific sites within the three-dimensional structure of cells (2). Cells are highly organized such that even the water in cells has a structure that is different from aqueous solutions (3). The carefully controlled environment inside mammalian cells facilitates the efficiency of metabolic processes.
Biomacromolecules from Marine Organisms and Their Biomedical Application
Se-Kwon Kim in Marine Biochemistry, 2023
A large marine environment is composed of microorganisms, plants and animals, which are a wealthy resource of unique natural products like macromolecules (peptides, carbohydrates, proteins, lipids). The macromolecules derived from organisms and their associated microbes are biomacromolecules validated in pharmaceutical research. Generally, bio-macromolecules from marine have been chemically diverse with antimicrobial activity that used to develop drugs to control drug-resistant pathogens. Macromolecules are large molecules ranging from 100 to 10,000 mm in size and built by different types of subunits. The single subunits adhere to each other through covalent bonds to form large molecules. Generally, macromolecules are carbohydrates, proteins, lipids, extracellular polymeric substances and nucleic acids. Biomacromolecules from marine resource has a major impact on immunomodulatory drugs. The apoptosis of malignant tumor cell growth induced by marine bio-macromolecules, and it has an advanced mechanism against multidrug-resistant microbes (Nikaido, 2009). Bio-macromolecules have improved bioactive properties, which is considered a pillar of chemotherapy (Yahya et al., 2019). In addition, biomacromolecules produced by marine organisms are being increasingly investigated for several biomedical applications (d’Ayala et al., 2008; Silva et al., 2012a, 2012b). The present chapter discusses the research on marine macromolecules and their biological importance carried out mostly during the last few years. Different aspects of biomedical applications and advanced technology for drug delivery applications are also discussed.
Scaffold processing
Yoshinobu Onuma, Patrick W.J.C. Serruys in Bioresorbable Scaffolds, 2017
Poly(L-lactide) is a thermoplastic homopolymer produced by polymerization of a monomer comprised of L-lactide. Polymerization is the process of converting the L-lactide monomer molecules into a polymer. A polymer is a large molecule, or macromolecule, comprised of many repeating interconnected monomer subunits. Lactide is derived from lactic acid (2-hydroxypropanoic acid), which is formed by bacterial fermentation of dextrose. Poly(L-lactide) is produced by ring-opening polymerization using hydroxyls as initiators. The polymerized poly(L-lactide) is typically produced in the form of pellets that are converted into other shapes by extrusion, molding, or spinning processes.
Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy
Published in Journal of Drug Targeting, 2019
Kui Li, Hongqi Tian
Tumour cells express PD-L1 under the action of various cytokines, which is related to tumour immune escape. Because PD-L1 expression is closely related to tumourigenesis and invasion in vivo and in vitro resistance to T cell-mediated lysis, it acts as an anti-apoptotic factor in the development of cancer cells [53]. During cancer development, activation of the PD-1/PD-L1 immune pathway can indicate that the tumour cells are exhibiting an adaptive mechanism of resistance to tumour infiltration lymphocytes involved in the anti-tumour T cell immune response. A molecule that binds to the PD-1 receptor can block its interaction with the ligands PD-L1 and PD-L2, releasing the PD-1 pathway-mediated inhibition of tumour immune responses. Therefore, PD-1/PD-L1 immune checkpoint inhibitors that inhibit the interaction between the PD-1 expressed on activated T cells and the ligand PD-L1/PD-L2 expressed on tumour cells are believed to inhibit tumour T cell immune surveillance [54,55], leading to the T cell-mediated death of malignant cells.
In silico QSAR modeling to predict the safe use of antibiotics during pregnancy
Published in Drug and Chemical Toxicology, 2023
Feyza Kelleci Çelik, Gül Karaduman
Molecular descriptors are defined as mathematical representations of the properties of molecules created by algorithms. Molecular descriptors’ numerical values are utilized to quantitatively describe the chemical and physical information of the molecules (Chandrasekaran et al.2018). The appropriate descriptors chosen for each model may differ depending on the structure of the molecules and the expected toxicological effect. For example, it has been shown that among the prominent descriptors adopted in toxicity prediction applications, ‘molecular property’, ‘connectivity’, and ‘topological’ are the three most essential descriptors for toxicity prediction applications (Li 2020). Our study also included the descriptors in the Chi Connectivity Indices, Electrotopological State Indices (E-State), Constitutional Descriptors, and Molecular Fragments sections that contributed to creating the most successful model.
Tips for reading patents: a concise introduction for scientists
Published in Expert Opinion on Therapeutic Patents, 2018
Kate E. Donald, K. M. Mohibul Kabir, William A. Donald
Patents that disclose organic compositions may not contain an examples section. Instead, they commonly contain drawings of molecules in the detailed description section. Such drawings detail the structure of molecules (i.e. depict the full chemical structure with all elements identified). Often, this is done by depicting molecular structures with R groups cross referenced to chemical functional groups listed in the text of the specification (such a presentation of the molecule is called a Markush structure). Markush structures enable patentees to protect a broad range of molecules. However, they can be very complex and obfuscate the invention for the reader. Unfortunately, the authors have no hints for understanding Markush structures other than to carefully work your way through all the possible substituents of the structures presented. For some scientific databases (e.g. SciFinder Scholar), it is possible to search by chemical structure (or similar chemical structures) to locate patents that may be relevant.
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