About: Structure stability of DS-1-conjugated MDM2 as evaluated by root-mean-square deviation (RMSD) analysis. 

1YCR

Bibenzyl analogue DS-1 inhibits MDM2-mediated p53 degradation and sensitizes apoptosis in lung cancer cells

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Details.

Scientist
Thanyada Rungrotmongkol
Protein
MDM2 protein
Ligand
DS-1
Simulation Duration
100 ns
InChIKey
KCYFPZNMQOXMRS-IGMIWYCNSA-N
SMILES
C[C@@H]1[C@@H]([C@@H]([C@H]([C@@H](O1)OC(=O)[C@]23CCC(C[C@H]2C4=CC[C@@H]5[C@]6(CC[C@@H]([C@@]([C@@H]6CC[C@]5([C@@]4(C[C@H]3O)C)C)(C)C=O)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)C(=O)O)O)O[C@H]8[C@@H]([C@H]([C@@H](CO8)O)O)O)O[C@H]9[C@@H]([C@H]([C@H]([C@H](O9)CO)O)O)O)C)(C)C)O[C@H]1[C@@H]([C@@H]([C@H]([C@@H](O1)C)O[C@H]1[C@@H]([C@H]([C@@H](CO1)O)O[C@H]1[C@@H]([C@](CO1)(CO)O)O)O)O)O)O)O
Molecular Formula
C69H108O36
Protein Details
Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.
Ligand Details
DS-1 exhibited a cytotoxic effect and sensitized lung cancer cells to cisplatin-induced apoptosis. DS-1 caused a significant increase in the cellular level of p53 protein, while the active form of p53 (phosphorylation at Ser15) was unaltered. DS-1 treatment in combination with cisplatin could enhance activated p-p53 (Ser15) and p53 downstream signaling (Bax, Bcl-2, and Akt), leading to a higher level of apoptosis. 
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