ArticleCurrent medicinal chemistry2023
Comparative Dynamic Features of Apo and Bound MDM2 Protein Reveal the Mechanism of Inhibitor Recognition for Anti-Cancer Activity.
Article in Current medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed, 1 citations in OpenAlex.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMouse Double Minute 2 Homolog (MDM2) oncogenic protein is the principal cellular antagonist of the p53 tumor suppressor gene. Restoration of p53 activity by inhibiting the MDM2-P53 interactions at the molecular level has become the cornerstone of cancer research due to its promising anticancer effects. Natural medicinal products possess various chemical structures and represent an essential source for drug discovery. α-Mangostin (AM) and gambogic acid (G250) are plant-derived compounds that showed inhibitory effects on MDM2-P53 interactions in vitro and in vivo.
methodsDespite the many clinical studies which performed deeper insight about the molecular understanding of the structural mechanisms exhibited by α-Mangostin and Gambogic acid-binding to MDM2 remains critical. In this study, comparative molecular dynamics simulations were performed for each Apo and bound p53 and MDM2 proteins to shed light on the MDM2-p53 interactions and get a better understanding of the inhibition mechanisms.
resultsResults revealed atomistic interaction of AM and G250 within the MDM2-p53 interaction cleft. Both compounds mediate the interaction between the α-helix motifs of the p53 amino-terminal domain, which caused a significant separation between orthogonally opposed residues, specifically Lys8 and Gly47 residues of the p53 and MDM2, respectively. Contrasting changes in magnitudes were observed in per-residue fluctuation on AM and G250 (~0.04 nm and ~2.3 nm, respectively). The Radius of gyration (~0.03 nm and 0.04 nm, respectively), C-alpha deviations (~0.06 nm and 0.1 nm, respectively). The phenolic group of AM was found to establish hydrogen interactions with Glu28 and His96 residues of MDM2. The trioxahexacyclo-ring of G250 also forms hydrogen bond interactions with Lys51 and Leu26 residues of MDM2.
conclusionUtilizing the information provided on the inhibitory binding mode adopted by each compound in this study may further assist in the tailored designs for cancer therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.