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Medicinal Plants of China Focusing on Tibet and Surrounding Regions
Published in Raymond Cooper, Jeffrey John Deakin, Natural Products of Silk Road Plants, 2020
Jiangqun Jin, Chunlin Long, Edward J. Kennelly
Chemical constituents: Polysaccharides, mannitol, cordycepin (Figure 2.13), aminophenol ergosterol (Yue et al., 2013), adenosine, sterols, peptides (cordymin and myriocin), melanin, lovastatin, γ-aminobutyric acid, and cordysinins (Lo et al., 2013).
Involvement of Sphingolipid Metabolism Enzymes in Resveratrol-Mediated Cytotoxicity in Philadelphia-Positive Acute Lymphoblastic Leukemia
Published in Nutrition and Cancer, 2022
We treated SD1 and SUP-B15 cells with increasing concentrations of resveratrol, SKI II, PDMP and myriocin for 48–72 h to study anti-proliferative effects using MTT assay. As indicated in Figure 1, resveratrol reduced cell viability in a time- and dose-dependent manner. Time-dependent IC50 concentrations for SD1 cells were calculated as 43 and 37 µM (Figure 1A). Similarly, IC50 concentrations for SUP-B15 cells were 37 and 20 µM (Figure 1B). These results indicated that resveratrol may potently inhibit Ph + ALL cell proliferation. Inhibitors targeting SK and GCS also inhibited cell viability in a time- and concentration-dependent manner (Figure 2). Time-dependent IC50 concentrations were calculated as 6.6 and 4.5 µM for SKI II. IC50 values were 36 and 25 µM for PDMP in SD1 cells (Figure 2A). Similarly, IC50 concentrations were 4.5 and 2.3 µM for SKI II and 32 and 18 µM for PDMP in SUP-B15 cells (Figure 2B). On the other hand, myriocin did not affect the cell viability significantly for both cells (Figure 2A and B).
Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Xin Wang, Xin Yang, Xin Sun, Yi Qian, Mengyao Fan, Zhehao Zhang, Kaiyuan Deng, Zaixiang Lou, Zejun Pei, Jingyu Zhu
MIC determinations were finished via broth microdilution assay with myriocin and caspofungin used as positive inhibitor controls. All experimental fungus were provided by the Pathogenic Microorganism (toxin) Preservation Center of Chinese Academy of Medical Sciences, including four species of fungi and two drug-sensitive reference strains as follows: Aspergillus fumigates (CMCCC(F) A.1a), Cryptococcus neoformans (CMCCC(F) D.2a), Sporothrix (CMCCC(F) D.1a), Rhizopus oryzae (CMCCC(F) B.81a), Candida parapsilosis (ATCC22019) and Candida krusei (ATCC6258). Myriocin was prepared to 2 mg/mL solution in methanol and caspofungin was prepared to 5 mg/mL solution in water. Compounds WXP-001∼003 were dissolved in dimethyl sulfoxide (DMSO) to prepare stock solutions of 10 mg/mL concentration.
Preclinical discovery and development of fingolimod for the treatment of multiple sclerosis
Published in Expert Opinion on Drug Discovery, 2019
Claudia Volpi, Ciriana Orabona, Antonio Macchiarulo, Roberta Bianchi, Paolo Puccetti, Ursula Grohmann
Later on, studies provided first clues on the molecular mechanism of action of these compounds, reporting that myriocin (1) is able to inhibit serine palmitoyltransferase (SPT) [8], an enzyme involved in the biosynthesis of sphingolipids. Strikingly, FTY720 (3c) and compound 2d were found inactive in inhibiting SPT, thereby suggesting a different mechanism of immunosuppressive action for these compounds [9]. The structural similarity between FTY720 (3c) and sphingosine (4) prompted further studies to investigate whether other sphingolipid binding proteins could be targets of FTY720 (3c). As a result, much like sphingosine (4) and the relative product sphingosine 1-phosphate (6, S1P), FTY720 was found to be a substrate for SPHK leading to the formation of FTY720-phosphate (5) [10]. S1P (6) is a nanomolar (nM) agonist of a class of lipid sensing G-protein-coupled receptors (GPCRs), including five members that are termed S1P1–5 receptors. Accordingly, FTY720-phosphate (5) is the active metabolite of FTY720 and a potent agonist of all S1P receptors (S1PR), with the exception of S1P2R (Table 1) [11–14]. The lack of activity of FTY720-phosphate at the S1P2R is an important feature for its therapeutic benefit. Indeed, S1P2R activation is associated with several unwanted effects, including pathological angiogenesis, vascular leakiness, vasoconstriction, and increased vascular tone [15–18].