Next Article in Journal
Improved Prognostic Accuracy of NEWS2 Score with Triage Data in Adults with Bacterial Sepsis: A Retrospective Cohort Study
Previous Article in Journal
Evaluating Leucine, Isoleucine, and Valine Ratios in Mixed Cortical Cell Cultures Following Cortical Trauma: An In Vitro Assessment
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJTM
Volume 5
Issue 3
10.3390/ijtm5030043
ijtm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Epigallocatechin Gallate as a Targeted Therapeutic Strategy Against the JAK2V617F Mutation: New Perspectives for the Treatment of Myeloproliferative Neoplasms and Acute Myeloid Leukemia

by
Leidivan Sousa Da Cunha
1,†,
Isabelle Magalhães Farias
1,†,
Beatriz Maria Dias Nogueira
1,
Caio Bezerra Machado
1,
Flávia Melo Cunha De Pinho Pessoa
1,
Deivide De Sousa Oliveira
1,2,
Guilherme Passos de Morais
1,
André Pontes Thé
1,3,
Patrícia Maria Pontes Thé
4,
Manoel Odorico De Moraes Filho
1,
Maria Elisabete Amaral De Moraes
1 and
Caroline Aquino Moreira-Nunes
1,3,5,*
1
Clinical Genetics Laboratory, Drug Research and Development Center (NPDM), Department of Medicine, Federal University of Ceará, Fortaleza 60020-181, Brazil
2
Departament of Hematology, Fortaleza General Hospital (HGF), Fortaleza 60155-290, Brazil
3
Clementino Fraga Group, Central Unity, Genomics and Molecular Biology Laboratory, Fortaleza 90619-900, Brazil
4
Department of Pharmacy, Federal University of Ceará, Fortaleza 60020-181, Brazil
5
Brazilian Institute of Intelligence in Health, Research and Education, IBISPE, Fortaleza 60160-230, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Transl. Med. 2025, 5(3), 43; https://doi.org/10.3390/ijtm5030043
Submission received: 21 July 2025 / Revised: 27 August 2025 / Accepted: 9 September 2025 / Published: 15 September 2025
Browse Figures
Versions Notes

Abstract

The JAK2V617F mutation is a major molecular factor in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and has been increasingly associated with clonal progression to acute myeloid leukemia (AML), resulting in a poorer prognosis and resistance to conventional therapies. This study integrates a comprehensive literature review with bioinformatic approaches to investigate the potential inhibitory activity of Epigallocatechin Gallate (EGCG), a green tea polyphenol widely recognized for its antioxidant and anticancer properties, on the JAK2V617F mutation. Clinical data from case reports demonstrated heterogeneity in disease progression and frequent therapeutic failures. Molecular docking analysis using the Janus Kinase 2 (JAK2) protein structure (PDB ID: 6D2I) identified a high-affinity binding pocket for EGCG near the V617F mutation site. EGCG exhibited strong binding affinity (−9.2 kcal/mol), forming key interactions with residues Lys581, Ile559, and Leu680, suggesting allosteric modulation of the JH2 pseudokinase domain. To validate our docking protocol, redocking of the known inhibitor AT9283 yielded a favorable Root Mean Square Deviation (RMSD) 2.683 Å and binding energy (−8.3 kcal/mol), confirming the reliability of our approach. Notably, EGCG demonstrated superior binding affinity compared to AT9283 and targets a distinct allosteric site, highlighting its unique mechanism of action and potential as a selective allosteric inhibitor. These findings position EGCG as a promising candidate for future preclinical evaluation, offering a novel strategy to overcome therapy resistance in JAK2V617F-driven malignancies.
Keywords: Janus kinase 2; acute myeloid leukemia; myeloproliferative neoplasms; catechin and bioinformatics Janus kinase 2; acute myeloid leukemia; myeloproliferative neoplasms; catechin and bioinformatics

Share and Cite

MDPI and ACS Style

Cunha, L.S.D.; Farias, I.M.; Nogueira, B.M.D.; Machado, C.B.; Pessoa, F.M.C.D.P.; Oliveira, D.D.S.; de Morais, G.P.; Thé, A.P.; Thé, P.M.P.; Moraes Filho, M.O.D.; et al. Epigallocatechin Gallate as a Targeted Therapeutic Strategy Against the JAK2V617F Mutation: New Perspectives for the Treatment of Myeloproliferative Neoplasms and Acute Myeloid Leukemia. Int. J. Transl. Med. 2025, 5, 43. https://doi.org/10.3390/ijtm5030043

AMA Style

Cunha LSD, Farias IM, Nogueira BMD, Machado CB, Pessoa FMCDP, Oliveira DDS, de Morais GP, Thé AP, Thé PMP, Moraes Filho MOD, et al. Epigallocatechin Gallate as a Targeted Therapeutic Strategy Against the JAK2V617F Mutation: New Perspectives for the Treatment of Myeloproliferative Neoplasms and Acute Myeloid Leukemia. International Journal of Translational Medicine. 2025; 5(3):43. https://doi.org/10.3390/ijtm5030043

Chicago/Turabian Style

Cunha, Leidivan Sousa Da, Isabelle Magalhães Farias, Beatriz Maria Dias Nogueira, Caio Bezerra Machado, Flávia Melo Cunha De Pinho Pessoa, Deivide De Sousa Oliveira, Guilherme Passos de Morais, André Pontes Thé, Patrícia Maria Pontes Thé, Manoel Odorico De Moraes Filho, and et al. 2025. "Epigallocatechin Gallate as a Targeted Therapeutic Strategy Against the JAK2V617F Mutation: New Perspectives for the Treatment of Myeloproliferative Neoplasms and Acute Myeloid Leukemia" International Journal of Translational Medicine 5, no. 3: 43. https://doi.org/10.3390/ijtm5030043

APA Style

Cunha, L. S. D., Farias, I. M., Nogueira, B. M. D., Machado, C. B., Pessoa, F. M. C. D. P., Oliveira, D. D. S., de Morais, G. P., Thé, A. P., Thé, P. M. P., Moraes Filho, M. O. D., Moraes, M. E. A. D., & Moreira-Nunes, C. A. (2025). Epigallocatechin Gallate as a Targeted Therapeutic Strategy Against the JAK2V617F Mutation: New Perspectives for the Treatment of Myeloproliferative Neoplasms and Acute Myeloid Leukemia. International Journal of Translational Medicine, 5(3), 43. https://doi.org/10.3390/ijtm5030043

Article Metrics

Back to TopTop