Review
Chemistry, Medicinal
Xin Jin, Rilei Yu, Xuemin Wang, Christopher G. Proud, Tao Jiang
Summary: MNKs phosphorylate eIF4E, playing a crucial role in cancer and metabolic diseases. Inhibitors of MNKs can be used for the treatment of various cancers, including solid tumors and leukemia.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Yuanyuan Zhu, Changying Wang, Mingqun Li, Xiaoyu Yang
Summary: This study demonstrated that Cercosporamide could effectively overcome chemoresistance in cervical cancer by targeting eIF4E via MNK inhibition. The drug showed preferential inhibition on cancer cells compared to normal cells, leading to enhanced efficacy of doxorubicin and cisplatin both in vitro and in vivo.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Qi Zhang, Hui Li, Quan Li, Qiyan Hu, Bo Liu
Summary: This study reveals for the first time that eIF4E expression and activity are upregulated in anlotinib-resistant NSCLC cells, and depletion of eIF4E significantly inhibits proliferation and induces apoptosis in resistant cells. Additionally, we found that cercosporamide, an MNK-dependent eIF4E inhibitor, can overcome anlotinib resistance and enhance its efficacy in non-resistant NSCLC cells. The importance of these findings is further supported by consistent results from in vivo and in vitro experiments.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Candice Mazewski, Leonidas C. Platanias
Summary: In leukemia, resistance to therapy is a major concern for survival. MAPK-interacting kinases (MNKs) have emerged as important activators of oncogenic-related signaling and potential mediators of resistance. Recent studies have shown promising preclinical efficacy of MNK inhibitors in combination formats or for treating chemotherapy-resistant cells, suggesting potential for use in clinical trials.
ONCOTARGETS AND THERAPY
(2023)
Article
Chemistry, Medicinal
Weijun Xu, Srinivasaraghavan Kannan, Chandra S. Verma, Kassoum Nacro
Summary: MNK1/2 are central enzymes activated by ERK or p38 MAP kinases, coordinating cellular signaling and regulating cell proliferation and survival. Overexpression of MNK1/2 and/or eIF4E is associated with diseases including cancer, neurological disorders, autism, and inflammation. There are ongoing efforts to develop potent and selective inhibitors of MNK1/2 in both academia and industry.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Shuo Li, Jia-shu Chen, Xiangqian Li, Xiaoyi Bai, Dayong Shi
Summary: Overexpression of eIF4E is common in various solid tumors and hematologic cancers, making it a potential anti-cancer target. This review provides a detailed classification and description of the anti-cancer activities of promising compounds, concluding that MNK1/2 and eIF4E/eIF4G interaction inhibitors are superior to mTOR inhibitors for targeted therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xueju Qi, Shuna Zhang, Zekun Chen, Lijun Wang, Wenyong Zhu, Chuanjin Yin, Junting Fan, Xiaochen Wu, Jing Wang, Chuanlong Guo
Summary: eIF4E plays a key role in regulating tumor growth and angiogenesis in lung cancer. Compound EGPI-1 inhibits the proliferation of lung cancer cells without affecting normal cells. It interferes with the eIF4E/eIF4G interaction and inhibits the Ras/MNK/ERK/eIF4E signaling pathway. Moreover, it exhibits anti-angiogenic activity. EGPI-1 shows promise as a novel anti-lung cancer drug.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Cell Biology
Dorota Gil, Marta Zarzycka, Joanna Pabijan, Ma lgorzata Lekka, Joanna Duli Dulinska-Litewka
Summary: Melanoma is resistant to chemotherapy and lacks fully effective targeted therapies. The mutations in melanoma lead to the hyperactivation of the MAPK and PI3K/AKT/mTOR pathways, which are responsible for abnormal protein synthesis. In this study, we investigated the effects of a specific PI3K/mTOR inhibitor, dactolisib, and Mnk inhibitor -CGP57380, alone and in combination on human melanoma cell lines. Both drugs showed inhibition of cell proliferation and migration when used individually, but their combination had additional antitumor effects. Simultaneous inhibition of both pathways may help overcome drug resistance.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Multidisciplinary
Yuanyuan Li, Jianming Xiong, Wenjing Guo, Yangye Jin, Wenjun Miao, Cong Wang, Hongman Zhang, Yi Hu, He Huang
Summary: The novel black phosphorus (BP) nanosheets-based nano-assembly CBPH shows great potential for delivering cisplatin and inhibiting tumor growth as well as lung metastasis in TNBC, by releasing cisplatin in response to internal and external stimuli in the tumor microenvironment. In vitro experiments indicate potent antitumor effects of CBPH through increased intracellular content of Pt and Pt-DNA adduct, which is further enhanced by NIR light exposure. Moreover, CBPH treatment exhibits significantly decreased migration, invasion and regrowth ability of tumor cells, highlighting its promising role in breast cancer therapy.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Ning Tang, Hanhui Li, Lihong Zhang, Xueyun Zhang, Yanni Chen, Hao Shou, Shuaishuai Feng, Xinhua Chen, Yan Luo, Ruikang Tang, Ben Wang
Summary: The newly developed drug can selectively induce biogenic mineral formation on tumor cells by absorbing calcium from the blood, thus inhibiting tumor growth and significantly improving the survival rates of mice.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Oncology
Yulin Xu, Shichong Liao, Lijun Wang, Yuan Wang, Wen Wei, Ke Su, Yi Tu, Shan Zhu
Summary: Galeterone shows potential therapeutic options in targeting breast cancer cells by suppressing MNK-eIF4E and beta-catenin, enhancing the effects of chemotherapeutic drugs, and providing a new direction for the treatment of breast cancer.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiaolin Yang, Zhenyang Liu, Xianli Yin, Yidong Zeng, Geyang Guo
Summary: Aberrant activation of eIF4E contributes to gastric cancer growth and resistance. Tomivosertib, a dual MNK1/2 inhibitor, enhances the sensitivity of gastric cancer to chemotherapy by suppressing MNK-eIF4E-beta-catenin. This study provides preclinical evidence for clinical trials using tomivosertib in combination with chemotherapy for gastric cancer.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Xin Jin, Tingting Qiu, Jianling Xie, Xianfeng Wei, Xuemin Wang, Rilei Yu, Christopher Proud, Tao Jiang
Summary: A series of novel MNK inhibitors were reported in this study, among which compound 18 showed potent inhibition of eIF4E phosphorylation in various cancer cell lines. Compound 18 selectively targeted MNK2, decreased the levels of key proteins, arrested the cell cycle, inhibited cell migration, and suppressed the secretion of cytokines. It represents a starting compound for further design of selective MNK inhibitors and their applications in other diseases.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Xin Jin, Maowei Li, Tingting Qiu, Rilei Yu, Tao Jiang
Summary: In this study, hit compounds targeting MNK1 and MNK2 were identified using the MarineChem3D database. The compounds from the phorbazole family showed good interaction with MNK1. Further analysis led to the design and synthesis of 29 derivatives, of which six compounds exhibited good inhibition against MNKs. The study also confirmed the vital interactions between these compounds and MNK1, providing important information for developing MNK inhibitors based on this structural class.
Review
Pharmacology & Pharmacy
Dan Zhang, Lin Liu, Jian Wang, Hong Zhang, Zhuo Zhang, Gang Xing, Xuan Wang, Minghua Liu
Summary: Nanoparticles based on PLGA and PEG-PLGA have been extensively studied for drug delivery in cancer treatment. These nanoparticles can encapsulate and release various drugs, and their surface can be modified with ligands for active tumor targeting. This review provides an overview of the synthesis, application, and recent advances of PEG-PLGA nanoparticles in cancer treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Analytical
Maria Vergara-Barberan, Maria Jesus Lerma-Garcia, Ernesto F. Simo-Alfonso, Marta Garcia-Hernandez, M. Elena Martin, Ana Garcia-Sacristan, Victor M. Gonzalez, Jose Manuel Herrero-Martinez
Summary: In this study, DNA aptamers with high binding affinity to the major allergen of olive pollen, Ole e 1, were selected using SELEX method. The binding of the aptamers was confirmed by ELONA and aptaprecipitation assays. Aptamer-modified capillary chromatography demonstrated the selective recognition of Ole e 1 against non-target proteins. The stability and reproducibility of the aptamer-modified monolithic column were suitable for practical applications.
ANALYTICA CHIMICA ACTA
(2022)
Article
Dermatology
Maria del Carmen de Arriba, Geronimo Fernandez, Esteban Chacon-Solano, Manuel Mataix, Lucia Martinez-Santamaria, Nuria Illera, Rebeca Carrion-Marchante, Maria Elena Martin, Fernando Larcher, Victor M. Gonzalez, Marcela Del Rio, Marta Carretero
Summary: This study generated aptamers that specifically recognize and modulate the function of FPR2 involved in wound repair. These aptamers act as FPR2 agonists and have demonstrated potential therapeutic value in wound healing.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Medicine, Research & Experimental
C. Pinto-Diez, R. Ferreras-Martin, R. Carrion-Marchante, J. Klett-Mingo, M. Garcia-Hernandez, M. Perez-Morgado, S. Sacristan, M. Barragan, M. Seijo-Vila, I Tundidor, S. Blasco-Benito, E. Perez-Gomez, I Gomez-Pinto, C. Sanchez, C. Gonzalez, V. M. Gonzalez, M. E. Martin
Summary: Breast cancer is the most common and deadly cancer for women worldwide. In this study, a specific aptamer called apMNKQ2 was optimized and shown to inhibit the proliferation, colony formation, migration, and invasion of breast cancer cells. It also demonstrated efficacy in reducing tumor volume and metastasis in mouse models.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Oncology
Jose Ignacio Klett-Mingo, Celia Pinto-Diez, Julio Cambronero-Plaza, Rebeca Carrion-Marchante, Miriam Barragan-Usero, Maria Isabel Perez-Morgado, Eulalia Rodriguez-Martin, Maria del Val Toledo-Lobo, Victor M. Gonzalez, M. Elena Martin
Summary: Lung cancer is a major cause of death worldwide and is the most common type of cancer. In this study, aptamers with high affinity and specificity for histone acetyltransferase 1 (HAT1) were obtained using the systematic evolution of ligands through the exponential enrichment (SELEX) approach. The apHAT610 aptamer, in particular, reduced cell viability, induced apoptosis and cell cycle arrest, and inhibited colony formation in lung cancer cell lines. These results suggest that the apHAT610 aptamer has potential as a drug for the treatment of lung cancer.
Article
Clinical Neurology
Macarena Hernandez-Jimenez, Francisco Abad-Santos, Ian Cotgreave, Jaime Gallego, Bernd Jilma, Alan Flores, Tudor G. Jovin, Jose Vivancos, Maria Hernandez-Perez, Carlos A. Molina, Joan Montaner, Joaquin Casariego, Mads Dalsgaard, David S. Liebeskind, Erik Cobo, Mar Castellanos, Pere Cardona Portela, Jaime Masjuan, Francisco Moniche, Jose Ignacio Tembl, Mikel Terceno Izaga, Juan F. Arenillas, Patricia Callejas, Jean Marc Olivot, Lionel Calviere, Hilde Henon, Mikael Mazighi, David Pineiro, Marco Pugliese, Victor M. Gonzalez, Maria Angeles Moro, Alvaro Garcia-Tornel, Ignacio Lizasoain, Marc Ribo
Summary: The study aimed to assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. The results showed that administering 0.2 mg/kg of ApTOLL within 6 hours in combination with EVT was safe and associated with a reduction in mortality and disability at 90 days compared with placebo.
Editorial Material
Medicine, Research & Experimental
M. Elena Martin
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Pharmacology & Pharmacy
Rebeca Carrion-Marchante, Celia Pinto-Diez, Jose Ignacio Klett-Mingo, Esther Palacios, Miriam Barragan-Usero, M. Isabel Perez-Morgado, Manuel Pascual-Mellado, Sonia Alcala, Laura Ruiz-Canas, Bruno Sainz Jr, Victor M. Gonzalez, M. Elena Martin
Summary: Lung cancer is a major cause of cancer-related death worldwide. A previously identified aptamer, apMNKQ2, showed promising results as an antitumor drug in breast cancer. This study investigates the antitumor potential of apMNKQ2 in non-small cell lung cancer where MNK1 plays a significant role.
Article
Oncology
Vladimir Mulens-Arias, Yadileiny Portilla, Sonia Perez-Yaguee, Raquel Ferreras-Martin, M. Elena Martin, Victor M. Gonzalez, Domingo F. Barber
Summary: Triple-negative breast cancer (TNBC) is a difficult subtype to treat and overactivation of MNK1 has been associated with tumor aggressiveness. This study showed that polyethyleneimine-coated iron oxide nanoparticles (PEI-IONPs) could enhance the intracellular delivery of an MNK1-specific aptamer, resulting in reduced MNK1 signaling and inhibiting TNBC cell migration in vitro. However, the antitumor effect of the aptamer-PEI-IONP complex was compromised in vivo due to minimal accumulation of IONPs in the tumor.
CANCER NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rafael Colmenares, Rebeca Carrion-Marchante, M. Elena Martin, Laura Salinas Munoz, Maria Laura Garcia-Bermejo, Juan C. Oller, Antonio Munoz, Francisco Blanco, Jaime Rosado, Ana I. Lozano, Sofia alvarez, Feliciano Garcia-Vicente, Gustavo Garcia
Summary: The impact of intraoperative radiotherapy electron beams with varying energy spectra and intensities on biological damage was assessed by analyzing the survival fraction of epithelial HaCaT cells. The cells were irradiated at different depths in water using nominal 6 MeV electron beams while consistently delivering a dose of 5 Gy to the cell layer. A Monte Carlo simulation was performed to evaluate the molecular damage induced by the radiation. The simulation results showed a significant agreement with the experimentally derived damage, indicating an increased damage as the incident electron energy and intensity decreased for a constant absorbed dose.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Microbiology
Sara M. M. Robledo, Silvia Perez-Silanes, Celia Fernandez-Rubio, Ana Poveda, Lianet Monzote, Victor M. Gonzalez, Paloma Alonso-Collado, Javier Carrion
Summary: In 2020, the WHO established a road map for neglected tropical diseases 2021-2030, aiming to control and eradicate 20 diseases including leishmaniosis and Chagas disease. The WHO has also been developing a Global Action Plan on Antimicrobial Resistance since 2015. Natural peptide molecules (AMPs and CPPs) show promise as alternative therapies for neglected zoonoses by improving efficacy while avoiding toxicity and resistance. Encapsulation and functionalization methods are being used to overcome limitations of antimicrobial peptides for approval in clinical programs against leishmaniosis and Chagas disease.
Article
Chemistry, Multidisciplinary
Jenifer Garcia-Fernandez, Laura Rivadulla Costa, Celia Pinto-Diez, M. Elena Martin, Victor M. Gonzalez, Maria de la Fuente Freire
Summary: Breast cancer is a complex and heterogeneous disease with high mortality rate. Recent research has focused on identifying new therapeutic targets, with protein kinase MNK1b being a promising candidate. An aptamer called apMNK2F has shown specific interaction with MNK1b, leading to significant reduction in tumor cell proliferation. However, aptamers cannot penetrate cell membranes, so suitable vectors are needed for intracellular delivery. In this study, vitamin E and sphingomyelin nanoemulsions were covalently conjugated with apMNK2F to facilitate intracellular delivery. The nanosystems successfully delivered the therapeutic aptamer, resulting in decreased breast cancer cell proliferation.
Review
Immunology
William Serumula, Geronimo Fernandez, Victor M. Gonzalez, Raveen Parboosing
Summary: This review discusses the targets and challenges of anti-HIV aptamer research and summarizes the prospects of this therapeutic strategy in the context of HIV infection.
CURRENT HIV RESEARCH
(2022)
