Department: Bioquímica y Biología Molecular

Research Unit: Instituto de Biotecnología y Salud (IDiBE)

Web page:

http://umh.es/contenido/Universidad/:persona_4203/datos_es.html

https://ibmc.umh.es/encinar.asp

Research Fields:

– My research interests focus on the application of computational methods to identify compounds capable of modulating the activity of proteins with biomedical relevance, including those implicated in cancer, obesity, and diabetes. I employ a range of in silico techniques—such as molecular modeling, molecular docking, and molecular dynamics simulations—together with scaffold-hopping strategies and ADMET profiling, to perform high-throughput virtual screening of chemical libraries. The resulting candidate compounds are subsequently subjected to experimental validation.

 Representative Publications:

• A Novel beta-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy. García-Yagüe, A.J., Cañizares-Moscato, L., Encinar, J. A., Cazalla, E., Fernández-Ginés, R., Escoll, M., Rojo, A. I. and Cuadrado, A. Journal of Biomedical Science, 32, 65 (2025). DOI: 10.1186/s12929-025-01157-3
• Silibinin is a suppressor of the metastasis-promoting transcription factor ID3. Verdura, S., Encinar, J.A., Gratchev, A., Llop-Hernández, A., López, J., Serrano-Hervás, E., Teixidor, E., López-Bonet, E., Martin-Castillo, B., Micol, V., Bosch-Barrera, J., Cuyàs, E., Menendez, J. A. Phytomedicine, 2024, 128, 155493. DOI: 10.1016/j.phymed.2024.155493
• Specific targeting of the NRF2/beta-TrCP axis promotes beneficial effects in NASH liver disease. Fernández-Ginés, R., Encinar, J.A., Escoll, M., Carnicero-Senabre, D., Jiménez-Villegas, J., García-Yagüe A.J., González-Rodríguez A., Garcia-Martinez, I., Valverde, A.M., Rojo, A.I., Cuadrado, A. Redox Biology, 69 (2024) 103027. DOI: 10.1016/j.redox.2024.103027
• PTPRK regulates glycolysis and de novo lipogenesis to promote hepatocyte metabolic reprogramming in obesity.  Eduardo H. Gilglioni, Ao Li, Wadsen St-Pierre-Wijckmans, Tzu-Keng Shen, Israel Perez-Chavez, Garnik Hovhannisyan, Michela Lisjak, Javier Negueruela, Valerie Vandenbempt, Julia Bauza-Martinez, Jose M. Herranz, Daria Ezerina, Stephane Demine, Zheng Feng, Thibaut Vignane, Lukas Otero Sanchez, Flavia Lambertucci, Alena Prasnicka, Jacques Deviere, David C. Hay, Jose Antonio Encinar, Sumeet Pal Singh, Joris Messens, Milos R. Filipovic, Hayley J. Sharpe, Eric Trepo, Wei Wu and Esteban N. Gurzov. Nature Communication 15, 9522 (2024). DOI: 10.1038/s41467-024-53733-0
• The Fatty Acid Synthase (FASN) signalome: A molecular guide for precision oncology.  Menendez, J.A.; Cuyàs, E.; Encinar, J.A.; Vander Steen, T.; Verdura, S.; Llop-Hernández, Á.; López, J.; Serrano-Hervás, E.; Osuna, S.; Martin-Castillo, B.; Lupu, R. Molecular Oncology, 2024, 18(3):479-516. DOI: 10.1002/1878-0261.13582
• Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors. Verdura, S., Encinar, J.A., Teixidor, E., Segura-Carretero, A., Micol, V., Cuyàs, E., Bosch-Barrera, J., Menendez, J.A. Cancers, 2022, 14(24), 6101. DOI: 10.3390/cancers14246101
• The current status and future prospects for therapeutic targeting of KEAP1-NRF2 and β-TrCP-NRF2 interactions in cancer chemoresistance. Srivastava, R., Fernández-Ginés, R., Encinar, J.A., Cuadrado, A., and Wells, G. Free Radical Biology and Medicine, 2022, 192, 246-260. DOI: 10.1016/j.freeradbiomed.2022.09.023
• Silibinin suppresses the hyperlipidemic effects of the ALK-tyrosine kinase inhibitor lorlatinib in hepatic cells. Verdura, S., Encinar, J.A., Fernández-Arroyo, S., Joven, J., Cuyàs, E., Bosch-Barrera, J., Menendez, J.A. International Journal of Molecular Sciences, 2022, 23(17), 9986. DOI: 10.3390/ijms23179986
• An inhibitor of interaction between the transcription factor NRF2 and the E3 ubiquitin ligase adapter β-TrCP delivers anti-inflammatory responses in mouse liver. Fernández-Ginés, R., Encinar, J.A., Hayes, J.D., Oliva, B., Rodríguez-Franco, M.I., Rojo, A.I., Cuadrado, A. Redox Biology 2022, 55, 102396. DOI: 10.1016/j.redox.2022.102396
• G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERΒ and ERΑ in pancreatic beta cells. Babiloni-Chust, I.; Dos Santos, R.S., Medina-Gali, R.M., Perez-Serna, A.A., Encinar, J.A., Martinez-Pinna, J., Gustafsson, J.A., Marroqui, L. and Nadal, A. Environment International 2022; 164,107250. DOI: 10.1016/j.envint.2022.107250
• Peimine, an anti-inflammatory compound from Chinese herbal extracts, modulates muscle-type nicotinic receptors. Alberola-Die, A.; Encinar, J.A.; Cobo, R.; Fernández-Ballester, G.; González-Ros, J.M.; Ivorra, I.; Morales, A. International Journal of Molecular Sciences 2021, 22, 11287. DOI: 10.3390/ijms222011287
• ERK5 Signaling Pathway Is A Novel Target Of Sorafenib: Implication In EGF Biology. Ortega-Muelas, M., Roche, O., Fernandez-Aroca, D., Encinar, J.A., Albandea Rodriguez, D., Arconada-Luque, E., Pascual-Serra, R., Muñoz, I., Sanchez-Perez, I., Belandia, B., Ruiz-Hidalgo, M. and Sanchez-Prieto, R. Journal of Cellular and Molecular Medicine. 2021; 25(22): 10591-10603. DOI: 10.1111/jcmm.16990
• Metformin Is a Pyridoxal-5′-phosphate (PLP)-Competitive Inhibitor of SHMT2. Tramonti, A., Cuyàs, E., Encinar, J.A., Pietzke, M., Paone, A., Verdura, S., Arbusà, A., Martin-Castillo, B., Giardina, G., Joven, J., Vazquez, A., Contestabile, R., Cutruzzolà F., and Menendez, J.A. Cancers. 2021, 13(16), 4009. DOI: 10.3390/cancers13164009
• Bisphenol-S and Bisphenol-F alter mouse pancreatic Β-cell ion channel expression and activity and insulin release through an estrogen receptor ERΒ mediated pathway. Marroqui, L., Martinez-Pinna, J., Castellano-Muñoz, M., dos Santos, R.S., Medina-Gali, R.M., Soriano, S., Quesada, I., Gustafsson, J., Encinar, J.A., and Nadal, A. Chemosphere. 2021; 265:129051. DOI: 10.1016/j.chemosphere.2020.129051

Patents:

1. Tratamiento de enfermedades relacionadas con NRF2. Solicitud de patente titulada “Treatment of NRF2-Related Diseases”, presentada el 15 de enero de 2021. Inventores: Antonio Cuadrado Pastor (45%), Raquel Fernández Ginés (15%), José Antonio Encinar (15%), Rafael León Martínez (5%), Juan Felipe Franco Gonzáles (5%), Manuel García López (5%), María Isabel Rodríguez Franco (5%) y Ana Isabel Rojo Sanchís (5%). El compuesto PHAR ha sido objeto de una solicitud de protección internacional (PCT/EP2022/050657; fecha de prioridad: 13 de enero de 2022) para su uso como inhibidor de la interacción proteína-proteína (PPI) β-TrCP/NRF2, con aplicación terapéutica en enfermedades hepáticas. La patente se encuentra actualmente licenciada a SERVATRIX S.L. Disponible en: WO2022152800A1
2. Uso de inhibidores de la proteína tirosina fosfatasa receptora kappa (PTPRK). Solicitud de patente titulada “Uses of Protein Tyrosine Phosphatase Receptor Kappa Inhibitors (PTPRK Inhibitors)”, presentada el 15 de noviembre de 2023 a nombre de la Université libre de Bruxelles y la Universidad Miguel Hernández de Elche. Número de solicitud: EP23383162.7. Presentada ante la Oficina Europea de Patentes (EPO) a través de la Oficina Española de Patentes y Marcas (OEPM). Inventores: Esteban Gurzov (33,5%), Eduardo Gilglioni (33,5%) y José Antonio Encinar (33%). Disponible en: WO2025104221A1
3. Compuestos identificados como inhibidores de CDK4 para uso como medicamentos. Solicitud de patente titulada “Compounds Identified as CDK4 Inhibitors for Use as Medicaments”, presentada el 2 de julio de 2024 a nombre de la Universidad Miguel Hernández de Elche y la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO). Número de solicitud: P202430551. Presentada ante la Oficina Europea de Patentes (EPO) a través de la Oficina Española de Patentes y Marcas (OEPM). Inventores: Camino de Juan Romero (25%), Miguel Saceda (25%), María Fuentes (7%), Salomé Araujo (2%), José Antonio Encinar (25%), María Pilar García (2%), Elizabeth Pérez (2%) y Ana María Fernández (2%). Disponible en: WO2026008907

Available Technologies:

1. Computational platform for the identification of protein–protein interaction (PPI) inhibitors (β-TrCP/NRF2 axis). Integrated in silico platform for the rational discovery of small-molecule inhibitors targeting protein–protein interfaces, with demonstrated application to the β-TrCP/NRF2 interaction. The workflow combines ensemble docking, pharmacophore modeling, and binding free energy estimation.

• Applications: Liver disease, oncology, oxidative stress-related disorders
• TRL: TRL 4–5 (validated in vitro with experimentally confirmed hits)
• IP linkage: Directly connected to the patented PHAR compound (PCT/EP2022/050657) and associated NRF2-targeting strategy.
• IP status: Patent + proprietary know-how
• Availability: Licensing and co-development (validated target-specific platform)

2. Advanced molecular similarity framework (ECFP/FCFP consensus approach). Computational pipeline integrating circular (ECFP) and feature-based (FCFP) fingerprints with consensus scoring to improve scaffold hopping and hit identification efficiency.

• Applications: Hit discovery, chemical space exploration, library design
• TRL: TRL 3–4 (proof-of-concept validated with internal and benchmark datasets)
• IP linkage: Enabling technology supporting compound identification in CDK4 and PTPRK inhibitor programs
• IP status: Proprietary know-how
• Availability: Collaborative development and integration into industrial pipelines

3. Predictive models for aquatic toxicity (LC50-based classification). Machine learning-based models for predicting aquatic toxicity in fish species, supporting regulatory frameworks and early hazard identification.

• Applications: REACH compliance, environmental risk assessment, safety-by-design
• TRL: TRL 4–5 (validated with curated experimental datasets)
• IP linkage: Cross-cutting tool applicable to all compound development pipelines (including patented series)
• IP status: Know-how + curated datasets
• Availability: Collaboration and regulatory-oriented partnerships

4. Integrated virtual screening and multi-parameter optimization pipeline. End-to-end computational workflow combining docking, molecular dynamics, rescoring, and ADMET filtering to identify and optimize lead compounds with reduced attrition risk.

• Applications: Drug discovery across kinase and phosphatase targets
• TRL: TRL 5 (validated in multiple real-case discovery campaigns)
• IP linkage: Directly contributed to the identification of compounds in CDK4 (P202430551) and PTPRK (7) patent applications
• IP status: Proprietary protocols + partial patent coverage via downstream compounds
• Availability: Co-development and industrial collaboration

5. Proprietary compound libraries and lead series (NRF2, CDK4, PTPRK). Design and development of focused chemical libraries and lead series targeting therapeutically relevant proteins, including kinase and phosphatase families.

• Applications: Oncology, metabolic and liver diseases
• TRL: TRL 4–6 (from hit validation to early preclinical candidates, depending on series)
• IP linkage:
  • NRF2 modulators → PCT/EP2022/050657
  • CDK4 inhibitors → P202430551
  • PTPRK inhibitors → 7
• IP status: Patented / under evaluation
• Availability: Licensing and co-development opportunities

6. Computational workflows for safety-by-design in drug development. Integrated computational strategies combining toxicity prediction, target profiling, and chemical optimization to minimize adverse effects early in the design phase.

• Applications: Safer drug development, regulatory science, green chemistry
• TRL: TRL 3–4 (methodological framework applied in multiple projects)
• IP linkage: Supports de-risking of patented compound series and increases translational potential
• IP status: Know-how
• Availability: Strategic collaboration (early-stage integration in pipelines)

These technologies form a coherent and vertically integrated drug discovery ecosystem, spanning from early computational design (TRL 3) to validated lead compounds with translational potential (TRL 5–6). Crucially, the platform has already generated protected intellectual property (three patent families) and licensed assets (e.g., NRF2 program), demonstrating a clear pathway from discovery to exploitation.

Company agreements: 

• Contrato para el estudio de la viabilidad de la producción de un edulcorante natural mediante procesos biotecnológicos NUTRAFUR SA.  15/03/2019-15/09/2020.