Nature‐Inspired MYC Inhibitor Disrupts MYC‐Driven Glycolysis and Restricts Ovarian Tumor Growth

Myelocytomatosis oncogene (MYC) inhibitors are not available for clinical applications because the MYC protein is not part of a receptor-ligand pair and lacks a defined binding site for small molecules. GD-07, drug-like small molecule identified throughcheminformatics that selectively binds to the G-quadruplex (G4) in the c-MYC promoter with high binding affinity and selectivity over dsDNA. NMR analysis reveals that GD-07 binds to the upper tetrad of c-MYC G4. It exhibits a favorable pharmacokinetic profile and high cytotoxicity in ovarian cancer (OC) cells (A2780) compared to the standard drug carboplatin. Normal cells show no sensitivity to GD-07, indicating a broad therapeutic window. GD-07 suppresses MYC expression, curbing glucose metabolism, and glycolysis while promoting p53 and proapoptotic markers in OC cells. In patient-derived OC organoids, GD-07 shows greater activity than carboplatin with promising clinical translatability.

Authors

Institutions

Publication Details

Journal
ChemMedChem
Published
2025-11-30
DOI
https://doi.org/10.1002/cmdc.202500554
Primary Topic
DNA and Nucleic Acid Chemistry
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Nature‐Inspired MYC Inhibitor Disrupts MYC‐Driven Glycolysis and Restricts Ovarian Tumor Growth

Vincenzo Canzonieri, Vinit Kumar, Flavio Rizzolio, D. Negi et al.
ChemMedChem
DNA and Nucleic Acid Chemistry
article

Nature‐Inspired MYC Inhibitor Disrupts MYC‐Driven Glycolysis and Restricts Ovarian Tumor Growth

Vincenzo Canzonieri, Vinit Kumar, Flavio Rizzolio, D. Negi, Bharathwaj Sathyamoorthy, Ankur Baliyan, Enrico Cavarzerani, Reshma Rani, Anubha Yadav, Sushil Kumar, Mamta Singh, Rajat Gupta, Umesh Singh, Akansha Dagar
article en

Abstract

Myelocytomatosis oncogene (MYC) inhibitors are not available for clinical applications because the MYC protein is not part of a receptor-ligand pair and lacks a defined binding site for small molecules. GD-07, drug-like small molecule identified throughcheminformatics that selectively binds to the G-quadruplex (G4) in the c-MYC promoter with high binding affinity and selectivity over dsDNA. NMR analysis reveals that GD-07 binds to the upper tetrad of c-MYC G4. It exhibits a favorable pharmacokinetic profile and high cytotoxicity in ovarian cancer (OC) cells (A2780) compared to the standard drug carboplatin. Normal cells show no sensitivity to GD-07, indicating a broad therapeutic window. GD-07 suppresses MYC expression, curbing glucose metabolism, and glycolysis while promoting p53 and proapoptotic markers in OC cells. In patient-derived OC organoids, GD-07 shows greater activity than carboplatin with promising clinical translatability.

ChemMedChemVol. 21(1)
Ca' Foscari University of Venice (IT), Indian Institute of Technology Bombay (IN), Indian Institute of Science Education and Research, Bhopal (IN), Yamanashi Research Institute (JP), Amity University (AE), Centro di Riferimento Oncologico (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Jubilant Life Sciences (India) (IN), Gautam Buddha University (IN), Yokohama City University (JP)
Openalex Percentile: Top 66%
DNA and Nucleic Acid Chemistry
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.