Article
Cell Biology
Vijaya Bharti, Reese Watkins, Amrendra Kumar, Rebecca L. Shattuck-Brandt, Alexis Mossing, Arjun Mittra, Chengli Shen, Allan Tsung, Alexander E. Davies, Walter Hanel, John C. Reneau, Catherine Chung, Gina M. Sizemore, Ann Richmond, Vivian L. Weiss, Anna E. Vilgelm
Summary: Inhibition of BCL-xL protein increases cell death in cancer cells treated with oncology drugs, improving therapeutic outcomes. This study reveals a crosstalk between the mitochondrial apoptotic pathway and cell cycle regulation, providing a new therapeutic target for cancers with wild-type p53.
Review
Chemistry, Medicinal
Naga Rajiv Lakkaniga, Zhengyu Wang, Yao Xiao, Anupreet Kharbanda, Li Lan, Hong-yu Li
Summary: Aurora Kinase B, as a therapeutic target for cancer treatment, has been studied for more than two decades. Inhibitors of Aurora Kinase B show promising biological results in vitro and in vivo experiments. Although no approved inhibitors for clinical use are available due to associated side effects, they exhibit excellent synergy with other treatment methods, making them a potential adjuvant therapy for difficult-to-treat cancers.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Dennis S. Metselaar, Aimee du Chatinier, Michael H. Meel, Giovanna ter Huizen, Piotr Waranecki, Joshua R. Goulding, Marianna Bugiani, Jan Koster, Gertjan J. L. Kaspers, Esther Hulleman
Summary: This study demonstrates the overexpression of AURKA and PLK1 in DMG and suggests that targeting these proteins simultaneously could be a potential therapeutic strategy for these pediatric brain tumors.
Article
Multidisciplinary Sciences
Xiaozhen Zhang, Xing Huang, Jian Xu, Enliang Li, Mengyi Lao, Tianyu Tang, Gang Zhang, Chengxiang Guo, Xiaoyu Zhang, Wen Chen, Dipesh Kumar Yadav, Xueli Bai, Tingbo Liang
Summary: The study reveals that NEK2 phosphorylates PD-L1 to maintain stability, impacting the efficacy of immunotherapy in pancreatic cancer, while NEK2 deficiency enhances lymphocyte infiltration and sensitivity to immunotherapy. Inhibiting NEK2 can enhance PD-L1 blockade, potentially improving the effectiveness of pancreatic cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Wei Yu, Jianwen Huang, Qichao Dong, Wenting Li, Lei Jiang, Qian Zhang, Li Sun, Shengtao Yuan, Xu He
Summary: Ag120, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, acts as an ASCT2 inhibitor in colorectal cancer cells. It blocks glutamine uptake and metabolism, leading to reduced cell proliferation, elevated autophagy, and increased oxidative stress, potentially through the ERK and mTOR signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Keli Lima, Livia Bassani Lins de Miranda, Anali Del Milagro Bernabe Garnique, Bruna Oliveira de Almeida, Mariane Cristina do Nascimento, Guilherme Augusto Sousa Alcantara, Glaucia Maria Machado-Santelli, Eduardo Magalhaes Rego, Joao Agostinho Machado-Neto
Summary: AD80, a multikinase inhibitor, exhibits antineoplastic effects in pancreatic cancer cells by reducing cell viability and inducing mitotic aberrations, autophagy, and apoptosis. The drug also modulates several genes and signaling pathways, providing insights into potential therapeutic strategies for pancreatic cancer.
Article
Oncology
Vishnu Kumarasamy, Paris Vail, Ram Nambiar, Agnieszka K. Witkiewicz, Erik S. Knudsen
Summary: This study identified that activation of RB and inhibition of CDK2 are determinants of sensitivity to pharmacologic CDK4/6 inhibitors. Additionally, protein levels of p27 are associated with cell cycle plasticity and sensitivity to CDK4/6 inhibition. The results suggest that targeting the plasticity of the cell cycle using a clinically applicable CDK2 inhibitor could be a viable treatment strategy.
Article
Oncology
Saiful Islam, Muhammed H. H. Rahaman, Mingfeng Yu, Benjamin Noll, Jennifer H. H. Martin, Shudong Wang, Richard Head
Summary: Rilpivirine, an anti-viral drug, has been shown to inhibit the growth of leukemia cells and has potential as a treatment for acute myeloid leukemia (AML).
Article
Oncology
Tufia C. Haddad, Vera J. Suman, Antonino B. D'Assoro, Jodi M. Carter, Karthik V. Giridhar, Brendan P. McMenomy, Katelyn Santo, Erica L. Mayer, Meghan S. Karuturi, Aki Morikawa, P. Kelly Marcom, Claudine J. Isaacs, Sun Young Oh, Amy S. Clark, Ingrid A. Mayer, Khandan Keyomarsi, Timothy J. Hobday, Prema P. Peethambaram, Ciara C. O'Sullivan, Roberto A. Leon-Ferre, Minetta C. Liu, James N. Ingle, Matthew P. Goetz
Summary: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase objective tumor response rates (ORRs) or progression-free survival (PFS) in endocrine-resistant metastatic breast cancer (MBC).
Article
Chemistry, Multidisciplinary
Guangqiong Xu, Qiao Weng, Lei Zhang, Yaye Song, Wenjun Zhan, Yuan Yin, Gaolin Liang, Fuqiang Wang
Summary: This study reports an AURKB-responsive hydrogel, Gel S/AZD, which enhances cervical tumor suppression by controlled release of AZD1152. Cell assays show that Gel S/AZD induces growth arrest and apoptosis of cervical cancer cells by downregulating the expression of AURKB downstream protein pH3. In vivo studies demonstrate that Gel S/AZD exhibits superior tumor suppressive effect in orthotropic cervical tumor models.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Nidhi Saini, Ajmer Singh Grewal, Viney Lather, Suresh Kumar Gahlawat
Summary: Phytochemicals contribute to protection and interaction processes by acting as antioxidants, anti-mutagens, anticarcinogens, and antimicrobial agents. In this study, sanguinarine was found to be the most potent inhibitor of epidermal growth factor receptor (EGFR) compared to erlotinib. Other alkaloids also showed potent inhibition against EGFR, but their stability with EGFR varied. Out of the 31 alkaloids subjected to ADMET prediction, 29 alkaloids followed Lipinski's rule of five and were predicted to have high bioavailability, low toxicity, and ease of synthesis.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Pharmacology & Pharmacy
Nehad M. Ayoub, Sara K. Jaradat, Kamal M. Al-Shami, Amer E. Alkhalifa
Summary: Angiogenesis plays a vital role in the growth and spread of solid cancers, but breast cancer has shown poor response to anti-angiogenic drugs. Assessing the angiogenic signaling mechanisms in breast cancer, exploring new drug targets, and improving treatment outcomes through vascular normalization and nanotechnology are important areas of research.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Wen Lu, Katarzyna M. Skrzypczynska, Arthur Weiss
Summary: Src-family kinases play different roles in T cell and B cell signaling, with their activity regulated by factors such as Csk. Csk is crucial for maintaining appropriate SFK activity levels and regulating PIP3 amounts to prevent inappropriate B cell activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Daniel Winardi, Pei-Yi Chu, Guan-Yu Chen, Ke Wang, Wei-Yu Hsu, Ching-Liang Hsieh, Yung-Hsiang Chen, Yang-Chang Wu, Juan-Cheng Yang
Summary: Fangchinoline, a natural compound, is identified as a potential adjuvant for ovarian cancer therapy by inhibiting Aurora A kinase activity and enhancing the efficacy of cisplatin treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Giuseppe Romeo, Federica Bonanno, Lisa L. Wilson, Emanuela Arena, Maria N. Modica, Valeria Pittala, Loredana Salerno, Orazio Prezzavento, Jay P. McLaughlin, Sebastiano Intagliata
Summary: The study focused on designing new benzylpiperazine derivatives with high affinity for sigma R-1 receptors and improved selectivity over sigma R-2 receptors. The compound 15 demonstrated potent antinociceptive effects in mouse models of inflammatory pain and neuropathic pain, without causing sedation or impairing locomotor responses, showing promise as a potential therapeutic for chronic pain.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Antonino N. Fallica, Valeria Pittala, Maria N. Modica, Loredana Salerno, Giuseppe Romeo, Agostino Marrazzo, Mohamed A. Helal, Sebastiano Intagliata
Summary: Sigma receptors have been found to play a significant role in cancer growth and cell proliferation. Recent research focuses on developing selective sigma receptor ligands with potential anti-tumor properties. Studies in medicinal chemistry provide insights into the structure-activity relationships of selective sigma receptor ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Anna Kaempffe, Stephan Dickgiesser, Nicolas Rasche, Andrea Paoletti, Elisa Bertotti, Ilse De Salve, Federico Riccardi Sirtori, Roland Kellner, Doreen Konning, Stefan Hecht, Jan Anderl, Harald Kolmar, Christian Schroeter
Summary: Appropriate selection of conjugation sites and technologies is crucial for the success of ADCs. This study systematically characterized ADCs conjugated by different methods to different positions, with noticeable differences in their PK profiles. The study confirms L328 and LC recognition motifs as favorable sites for conjugation and emphasizes the importance of early selection of suitable ADC candidates through PK analyses.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ibrahim M. El-Deeb, Valeria Pittala, Diab Eltayeb, Khaled Greish
Summary: The study found that the duocarmycin derivative tafuramycin A shows potential efficacy in TNBC treatment, with encapsulation in a micellar system helping to reduce side effects and increase drug accumulation in tumor tissues.
Article
Chemistry, Medicinal
Stefania Demuro, Conall Sauvey, Shailesh K. Tripathi, Rita M. C. Di Martino, Da Shi, Jose A. Ortega, Debora Russo, Beatrice Balboni, Barbara Giabbai, Paola Storici, Stefania Girotto, Ruben Abagyan, Andrea Cavalli
Summary: The human kinome plays a crucial role in various pathways and its dysregulation is associated with central nervous system-related disorders. Simultaneously modulating multiple protein kinases through pharmacological approaches may lead to superior therapeutic effects compared to traditional single target, single drug approaches.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Mohamed Haider, Amr Elsherbeny, Valeria Pittala, Valeria Consoli, Maha Ali Alghamdi, Zahid Hussain, Ghalia Khoder, Khaled Greish
Summary: Lung cancer is a major cause of cancer occurrence and mortality worldwide. Drug resistance is a complex process in lung cancer, and nanomedicine provides promising tools for reversing resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Veronica Redaelli, Alice Bosi, Fabio Luzi, Paolo Cappella, Pietro Zerbi, Nicola Ludwig, Daniele Di Lernia, John Vincent Roughan, Luca Porcu, Davide Soranna, Gianfranco Parati, Laura Calvillo
Summary: This study examined the potential adverse effects of acute restraint stress on mice, finding that non-aversive handling methods such as tunnel handling and mechanoceptive handling could mitigate these effects, including improving body weight maintenance and physiological responses. Additionally, restraint stress could lead to metabolic and behavioral changes, increasing the risk of bias.
Article
Biochemistry & Molecular Biology
Valeria Consoli, Valeria Sorrenti, Valeria Pittala, Khaled Greish, Agata Grazia D'Amico, Giuseppe Romeo, Sebastiano Intagliata, Loredana Salerno, Luca Vanella
Summary: Ferroptosis is suggested as a potential new strategy for treating breast cancer, particularly triple negative breast cancer. The study reveals the importance of HO in ferroptosis, with HO-1 induction potentially accelerating the process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Beatrice Balboni, Shailesh Kumar Tripathi, Marina Veronesi, Debora Russo, Ilaria Penna, Barbara Giabbai, Tiziano Bandiera, Paola Storici, Stefania Girotto, Andrea Cavalli
Summary: In this study, we identified promising GSK-3 beta inhibitors through 1D F-19 NMR fragment screening and biophysical assays. We also proposed an alternative screening workflow to overcome the limitations of common GSK-3 beta inhibitors and found selective inhibitors and/or inhibitors capable of modulating GSK-3 beta activity without complete inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valeria Ciaffaglione, Valeria Consoli, Sebastiano Intagliata, Agostino Marrazzo, Giuseppe Romeo, Valeria Pittala, Khaled Greish, Luca Vanella, Giuseppe Floresta, Antonio Rescifina, Loredana Salerno, Valeria Sorrenti
Summary: This paper presents a novel series of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, showing high inhibition against the BCR-ABL protein. Molecular docking studies revealed insights into the binding mode with different targets, providing a structural explanation for the varying activities of the compounds.
Review
Health Care Sciences & Services
Maha Ali Alghamdi, Antonino N. Fallica, Nicola Virzi, Prashant Kesharwani, Valeria Pittala, Khaled Greish
Summary: Personalized medicine and nanomedicine are both new concepts in medical practice. Personalized medicine aims to customize therapeutic management based on a patient's personal attributes, while nanomedicine applies nanotechnology advances in medicine for diagnosis and treatment. The integration of these two fields can provide more effective treatment options tailored to individual patients.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Shereen Morsi, Valeria Pittala, Mohammad Alqudah, Mohamed Haider, Khaled Greish
Summary: The study revealed that AgNPs have inhibitory effects on pain response and show dose-dependent behavior in animal models. The findings indicate that AgNPs can significantly increase the paw withdrawal threshold in animals with CCI.
Article
Multidisciplinary Sciences
Marta Stefania Semrau, Gabriele Giachin, Sonia Covaceuszach, Alberto Cassetta, Nicola Demitri, Paola Storici, Graziano Lolli
Summary: The crystallographic structure of the ternary complex PP1/PTG/carbohydrate is reported, and the mechanism of PTG-mediated PP1 recruitment to glycogen is further studied, including the unusual combination of recruitment sites, their contributions to the overall binding affinity, and the conformational heterogeneity of this complex.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lucia Longhitano, Giuseppe Broggi, Sebastiano Giallongo, Maria Failla, Lidia Puzzo, Teresio Avitabile, Daniele Tibullo, Alfio Distefano, Valeria Pittala, Michele Reibaldi, Guido Nicola Zanghi, Antonio Longo, Andrea Russo, Rosario Caltabiano, Giovanni Li Volti, Nicolo Musso
Summary: The study revealed the important role of HO-1 in regulating uveal melanoma progression, with an increase of HO-1 promoting cellular proliferation and wound healing ability of tumor cells, suggesting HO-1 protein expression may serve as a potential prognostic and therapeutic factor in UM patients.
Article
Pharmacology & Pharmacy
Luca M. Barbero, Andrea Di Ianni, Francesco Molinaro, Kyra J. Cowan, Federico Riccardi Sirtori
Summary: The characterization of Antibody-Drug Conjugates (ADCs) in preclinical in vivo and in vitro studies requires the development of various bioanalytical methods. This study presents a quantitative hybrid Ligand Binding/Liquid Chromatography High Resolution and Accuracy Mass Spectrometry (LB/LC-HRAM) method that can condense most of the necessary bioanalytical information in one method. It detects whole ADC molecules and has demonstrated reliable performance in plasma mouse samples. It also allows for the simultaneous detection of lower drug-to-antibody ratio (DAR) ADC species, enabling qualitative characterization of in vivo ADC conjugation.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
