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Biological Response Modifiers and Chemotherapeutic Agents that Alter Interleukin 2 Activities
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
William L. West, Allen R. Rhoads, Clement O. Akogyeram
Swainsonine, an indolizidine alkaloids, has generated interest in its potential use as an anticancer agent with reports that it: (i) inhibits tumor growth and metastasis (41), (ii) augments natural killer (NK) and macrophage-mediated tumor cell killing (42) and (iii) stimulates bone marrow cell proliferation (43). The antineoplastic activity of swainsonine can be explained, at least in part, by augmentation of immune effector mechanisms (44,45).
Structure, Function, and Regulation of Pulmonary Surfactant Proteins
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Jeffrey A. Whitsett, Timothy E. Weaver
The primary translation product of rat and human SP-A migrates with considerable size and charge heterogeneity.10–14 The heterogeneity of the human SP-A transcript is related, at least in part, to acetylation,40 but may also be related to the expression of more than one SP-A gene(s)16,17 or to other posttranslational processing. The primary translation product of human SP-A binds to and is internalized by pancreatic microsomes and is proteolytically processed by removal of the leader sequence in vitro. In rat type II epithelial cells, SP-A is synthesized and routed in a manner similar to other secretory proteins.30 SP-A is translated, the leader sequence is removed, and, depending upon the species, dolichol-mannose donor groups are added, providing one or two oligosaccharide chains to asparagine residues in the carboxy- and/or amino-terminal domains of the molecule. Partially processed, high-mannose forms are found in the proximal intracellular compartments (rough endoplasmic reticulum and Golgi apparatus), where they are subjected to processing by glucosidases and mannosidases.30 Swainsonine (a mannosidase inhibitor) and castanospermine (a glucosidase inhibitor) produce the expected, aberrantly processed precursor forms of SP-A which are both stored and secreted by type II cells.30,41
Glycoform-resolved pharmacokinetic studies in a rat model employing glycoengineered variants of a therapeutic monoclonal antibody
Published in mAbs, 2021
David Falck, Marco Thomann, Martin Lechmann, Carolien A. M. Koeleman, Sebastian Malik, Cordula Jany, Manfred Wuhrer, Dietmar Reusch
Additionally, the Man5G0 hybrid-type glycoform led to a strongly increased clearance in the Mono mAb experiment. Though one publication also demonstrated the faster clearance of hybrid-type structures compared to complex biantennary structures, therein a smaller effect size was observed as compared to Man5.19 In our study, the Man5G0 hybrid had an even higher clearance rate (4.7-fold increase) than Man5 (1.8 to 2.6-fold increase). However, the swainsonine-generated mAb used by Kanda et al. featured a mixture of Man5G0 and Man5G1 glycans.19 Maybe the (opposing) effect of galactose on clearance (see below) is more pronounced in these hybrid-types than in complex glycans. In summary, it seems that additional mannoses on top of the N-glycan core mannoses strongly increase clearance, even in the context of a hybrid-type glycoform.
Swainsonine inhibits proliferation and collagen synthesis of NIH-3T3 cells by declining miR-21
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Chao Li, Peipei Wang, Ziyang Fu, Yongtao Li, Shouju Li
Swainsonine (SW, CAS number: 72741–87-8, Figure 1) is an indolizidine alkaloid first discovered in Swainsona canescens and widely disturbed in a number of plants worldwide [6]. Currently, there are three pathways for SW production: isolation from infected plants, synthesis using chemical methods and fermentation from fungi [7]. Previous studies proved that SW could serve as a special inhibitor of α-mannosidase II in the Golgi complex to influence the synthesis of a number of carbohydrates, glycoproteins and glycolipids in cells, as well as reduce the concentration of oligosaccharides at the cell surface [7,8]. Chotai et al. reported that SW could uptake into normal human fibroblasts in culture [9]. Cenci et al. indicated that SW could induce the accumulation of mannose-rich oligosaccharides in human fibroblasts [10]. However, until now, no any literature is available concerning the effects of SW on fibroblasts proliferation and collagen synthesis.
Inhibitory activities of indolizine derivatives: a patent review
Published in Expert Opinion on Therapeutic Patents, 2020
Kamal M. Dawood, Ashraf A. Abbas
Indolizine (1) is a heteroaromatic ring that belongs to a class of bridgehead-N-fused heterocyclic systems. Indolizine is biostere for indole which is widely common in a large number of natural products, pharmaceuticals, and approved commercial drugs. Indolizine containing compounds have pronounced diverse biological properties and also employed in material science [123–4]. Hydrogenated indolizine (indolizidine) is a well-known core nucleus in many natural product alkaloids which are highly potent scaffolds for drug discovery [56789–10]. One of the most common bioactive indolizidine alkaloids is swainsonine (2) that had a potential chemotherapy drug [11] and toxicological properties [12131415–16] as well as therapeutic potentials [17181920–21]