
School of Medicine Publications and Presentations
Document Type
Article
Publication Date
12-12-2024
Abstract
Metarrestin (ML246) is a first-in-class pyrrole-pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in solid tumor cells. The occurrence of PNC demonstrates a positive correlation with malignancy, serving as an indicator of tumor aggressiveness, progression, and metastasis. Various promising preclinical results have led to the clinical translation of metarrestin into a first-in-human trial. This review aims to summarize (i) the current understanding of the structure and function of PNC and its role in cancer progression and metastasis, (ii) key findings from studies examining the effect of metarrestin on various cancers across the translational spectrum, including in vitro, in vivo, and human clinical trial studies, and (iii) the pharmaceutical relevance of metarrestin as a promising anticancer candidate. Furthermore, our molecular docking and MD simulation studies show that metarrestin binds to eEF1A1 and eEF1A2 with a strong and stable affinity and inhibits eEF1A2 more efficiently compared to eEF1A1. The promising results from preclinical studies suggest that metarrestin has the potential to revolutionize the treatment of cancer, heralding a paradigm shift in its therapeutic management.
Recommended Citation
Kashyap, V. K., Sharma, B. P., Pandey, D., Singh, A. K., Peasah-Darkwah, G., Singh, B., Roy, K. K., Yallapu, M. M., & Chauhan, S. C. (2024). Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis. Cells, 13(24), 2053. https://doi.org/10.3390/cells13242053
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Cells
DOI
https://doi.org/10.3390/cells13242053
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
© 2024 by the authors.
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).