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Enzyme-Releasing Peptide
Published in Jason Kelley, Cytokines of the Lung, 2022
Allen B. Cohen, Edmund J. Miller, Cassandra MacArthur
There are several ways in which investigators gain access to the biology and chemistry of peptide cytokines that have powerful actions at very low concentrations. The first way is to define a biological activity. This activity is the tool that is necessary to isolate the peptide and sequence the protein and, eventually, the gene. In the case of ERP, we were unable to isolate or sequence it. However, we were able to make a monoclonal antibody to it. The development of the antibody led to the development of a quantitative test for the ERP and the ability to use all of the other powerful analytical tools related to antibodies.
Drugs in pregnancy and lactation
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Safety evaluation programs include two relevant species in which the compound is pharmacologically active for detection of the embryo-fetal toxicity studies; one rodent and one non-rodent species are requested. Due to the placental similarities between humans and rodents or rabbits, the majority of the regulatory embryo-fetal toxicity studies are routinely performed in the rat and rabbit. The biological activity with species and/or tissue specificity of compounds should be considered. Some are biologically active in conventional toxicity species, while others have species-specific biological activity. Non-human primates are rarely used as alternative test species, since historical data are poor and the rate of spontaneous anomalies is often high. However, for biotechnology products when only one species can be identified or where the biological activity of the product is well understood, one relevant species may suffice. Toxicity studies in non-relevant species may be misleading and are discouraged.
Pharmogenology: The Industrial New Drug Development Process
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
The specific tests performed in isolated tissues, organ systems, or in whole animals are, of course, a direct reflection of the pharmaceutical company's therapeutic goals as earlier delineated. This is a most important concept which often eludes the uninitiated. The discovery of interesting and possibly therapeutically significant biological activity is a summation and evaluation of selected studies or tests done in the departments of microbiology, biochemistry, endocrinology, and pharmacology. These studies, tests, and screens are established to determine whether the molecules synthesized by the medicinal chemist have activity that will make them of interest for further study or for chemical synthetic analoging. However, this information is, of necessity, restricted by the nature of the biological tests, and these tests are restricted to the expressed areas of therapeutic interests and capabilities of the individual pharmaceutical company.
High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mazen Aseeri, José Luis Abad, Antonio Delgado, Gemma Fabriàs, Gemma Triola, Josefina Casas
Cell-based assays allow evaluating biological activity in a more physiologically relevant system that also considers additional factors that might have a positive impact on inhibitory potency such as permeabilization through cellular membranes, metabolisation or concentration by intracellular compartmentalisation. Thus, the activity of the nine selected hits was next examined in intact cells using AC overexpressing A375 cells and the fluorogenic substrate RBM14-C12. First, compounds were tested in a primary screening assay. Measurements were performed in triplicated at a single-point concentration of 20 µM. The results showed that only two of the 9 tested compounds exhibited a significant inhibition of AC activity at this concentration: W000113402_C12 with a 53% inhibition and W000113414_H19 with a weaker 32% inhibition, whereas slight effects were observed for the other hits (Figure 4(A)). Dose-dependent inhibition could be also confirmed for W000113402_C12 in the cell-based assay displaying an IC50 of value of 32 µM (24.3–44.7) (Figure 4(B)).
Effect of different molecular weight and terminal group PLGA on docetaxel nanoparticles: characterization and cytotoxic activity of castration-resistant prostate cancer cells
Published in Pharmaceutical Development and Technology, 2022
Basak Simitcioglu, Isik Didem Karagoz, Sibel Ilbasmis-Tamer, Ugur Tamer
PLGA is a copolymer approved by the FDA, which has been the subject of much research in terms of its usage in drug delivery systems due to its many superior properties. Different molecular weights and different terminal group compositions of PLGA were investigated to increase the encapsulation efficiency and to obtain small particle size of the nanoparticles. The drug-polymer compatibility resulted from the structure of polymer and drug and also drug Mw directly affects the properties of the NP formulation (Mittal et al. 2007). For this reason, it is necessary to consider these properties and biological activity of the drug, which affect its behavior. For this instance, drug carrier nanoparticles were prepared with PLGA resomers of DTX with different Mw groups (low Mw: RG 502 and RG 502H groups; high Mw: RG 504 and RG 504H groups) and different terminal groups (acid groups: RG 502H and RG 504H; ester groups: RG 502 and RG 504) in this study, as stated Figure 1. The prepared NP properties were investigated in terms of characterization and in vitro biological activities.
The evaluation of hepatoprotective effects of flavonoids from Scorzonera austriaca Wild against CCl4-induced acute liver injury in vitro and in vivo
Published in Drug and Chemical Toxicology, 2022
Enwei Wei, Sixi Zhang, Jinghui Zhai, Sitong Wu, Guangshu Wang
There is a known fact that biological activity is closely depended on the structure of substance. Taking flavonoid as an example, briefly, p-electron conjugation enhanced by 2,3-double bond at C ring and the presence of O-dihydroxy group at B ring could contribute to the antioxidant activity and the high stability, respectively (Deepha et al.2014). In addition, He et al. (2019) indicated that hydroxyl group at C3′ or C4′ of B ring had better hepatoprotective effect than that of non-hydroxy, two hydroxyl groups or methoxy groups. Therefore, it could be speculated that compound IV and compound VII should possess a better hepatoprotective effect. However, to obtain a wide application, it is imminent that we should determine the best compound among these compounds isolated from FSA and explore its relationship between the structure and hepatoprotective effect in our future research.