( B) Cell morphology after treatment with ZJ-101. Taken together, these findings implicate a unique mechanism of action for the family of superstolides and other related analogs. The disruption of glycosylation by ZJ-101 leads to pleiotropic effects on proliferation and adhesion, which synergize with etoposide in a 3D spheroid combination model. Through this analysis, we identified a selectivity for dysregulation of O-linked glycosylation, which primarily occurs within the Golgi apparatus. Transcriptomic and lectin stain imaging analyses further converged on a dysregulation of glycosylation within the endomembrane system. Cell cycle and growth rate analysis revealed a strong cytostatic effect. Notably, an anti-adhesive effect was identified, which was approximately 30-fold more potent than the previously described anti-proliferative effect. However, the mechanism of action of ZJ-101 and other analogs has remained unknown.Įmploying several phenotypic assays in cancer cell lines, we identified novel activities and phenotypes associated with ZJ-101 that have revealed a unique mechanism of action.
Subsequently, several analogs were produced with enhanced potency in the single-digit nanomolar range. In 2013, a truncated superstolide A was designed and synthesized (named ZJ-101) that maintains the potent anticancer activity of the original natural product, thereby solving the supply problem of superstolide A, albeit indirectly. However, the scarcity of natural products seriously hampered the biological investigation. The unprecedented chemical structures of this group of marine natural products suggest they might have a unique cellular target(s) and a novel mechanism of action.
isolated novel macrolides they termed superstolides A and B, which were subsequently shown to display anticancer activity. Originally identified during the 1874 voyage of the HMS Challenger expedition, the sponge was resurrected in the early 1990s when D’auria et al. Or you can use the Online Percentage Calculator.Neosiphonia Superstes is a species of marine sponge localized to the region of New Caledonia in the South Pacific.
Multiply resultant value by 100 to get a percentage score. 3) Join the X and Y axisĪs a result, we get 0.71566 4) Convert resultant value into percentage The second step is to look at the second decimal number on X-axis. Now we have to find out the corresponding probability from the table. In John's case, we will use the positive table because we get a positive z-score of 0.57. Similarly, if we get a negative z-score, then we will use the negative table. If we get a z-score positive then we will use a positive table. So, keep it handy.Īs we all know that there are two z-tables with positive and negative values. For that, we will use a Z-Table (or Standard Normal Distribution Table).
To check how well John performed, we need to find the percentage of highest and lowest scores of other students.
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