Article
Biology
Gayoung Jang, Jiyeon Kweon, Yongsub Kim
Summary: A universal pegRNA was developed in this study to correct all types of G12 and G13 oncogenic KRAS mutations using CRISPR-mediated prime editors (PEs). The universal pegRNA successfully corrected 12 types of KRAS mutations with up to 54.8% correction frequency in HEK293T/17 cells. Endogenous KRAS mutations in human cancer cells, specifically G13D KRAS mutation, were also successfully corrected to wild-type KRAS sequences with up to 40.6% correction frequency without indel mutations. The findings suggest the potential of utilizing prime editing with the universal pegRNA as a "one-to-many" therapeutic strategy for KRAS oncogene variants.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Anouke van Rumund, Lukas Pavelka, Rianne A. J. Esselink, Ben P. M. Geurtz, Ron A. Wevers, Brit Mollenhauer, Rejko Krueger, Bastiaan R. Bloem, Marcel M. Verbeek
Summary: The study found that Parkinson's disease patients using peripheral decarboxylase inhibitors had elevated serum AADC enzyme activity, which may lead to the need for increased levodopa dosage to maintain therapeutic effects.
NPJ PARKINSONS DISEASE
(2021)
Review
Pharmacology & Pharmacy
Mireia Sueca-Comes, Elena Cristina Rusu, Anna M. Grabowska, David O. Bates
Summary: The number of cancer drugs is increasing, but most research is still focused on a small subset of well-studied targets, with limited investigations into poorly studied kinases.
PHARMACOLOGICAL REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Francis Giraud, Elisabeth Pereira, Fabrice Anizon, Pascale Moreau
Summary: This review emphasizes the role of protein kinases as potential biological targets in pain management, categorizing them into different groups in the human kinome and describing examples of small molecule inhibitors demonstrating analgesic effects. It highlights the fundamental role that protein kinase inhibitors could play in the development of new pain treatments.
Review
Chemistry, Medicinal
Tiandi Ding, Ying Zhi, Weilin Xie, Qingqiang Yao, Bo Liu
Summary: Sphingosine kinases are lipid kinases that phosphorylate sphingosine to sphingosine-1-phosphate, playing a role in regulating biological processes; targeting their signaling pathway is a potential treatment strategy for various pathophysiological conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Marino Paroli, Rosalba Caccavale, Maria Pia Paroli, Luca Spadea, Daniele Accapezzato
Summary: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine, peripheral joints, and entheses. Biologic therapies that selectively block cytokines have shown effectiveness in treating the disease, but some patients do not respond well to these treatments. Synthetic molecules that inhibit Janus kinases (JAK) have been used to treat rheumatoid arthritis and other inflammatory rheumatic diseases. This review aims to discuss the efficacy and safety of these molecules in axSpA therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Oncology
Michelle C. Barton, Guillermina Lozano
Summary: This study reveals that sustained activation of p53 leads to hepatocyte loss, expansion of hepatic progenitor cell population, and tumor development in mice. Similar phenomenon is observed in chronic liver disease in humans. The findings highlight the complexity and non-cell autonomous nature of p53 response.
Article
Biochemistry & Molecular Biology
ShaSha Wang, Yidan Huo, Jinmiao Zhang, Longfei Li, Fei Cao, Yali Song, Yajing Zhang, Kan Yang
Summary: Targeting sphingosine kinase 2 (SphK2) has been identified as a novel strategy for cancer treatment. However, there is a lack of potent and selective SphK2 inhibitors. In this study, a series of novel SphK2 inhibitors were designed, synthesized, and screened, with compound 12e showing the strongest inhibitory activity. Molecular dynamics simulations were performed to analyze the detailed interactions between SphK2 and its inhibitors. In addition, 12e exhibited anti-proliferative activity in various cancer cells and inhibited the migration of MCF-7 breast cancer cells.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Suneeta Devi, Anna E. Carberry, Greice M. Zickuhr, Alison L. Dickson, David J. Harrison, Rafael G. da Silva
Summary: DNPH1 catalyzes the N-ribosidic bond cleavage of 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate to generate 2-deoxyribose 5-phosphate and 5-hydroxymethyluracil. The crystal structures of unliganded DNPH1 and DNPH1 bound with 2'-deoxyuridine 5'-monophosphate were solved, revealing the interaction between the catalytic Glu residue and a conserved Tyr residue. Functional data supported the proposed mechanism, with hydrolysis of dUMP confirmed by liquid chromatography-mass spectrometry analysis. The pH-rate profile and solvent isotope effects provided insights into the catalytic mechanism.
Review
Chemistry, Medicinal
Maria Antonietta Occhiuzzi, Gernando Lico, Giuseppina Ioele, Michele De Luca, Antonio Garofalo, Fedora Grande
Summary: The PI3K/PKB/mTOR signaling pathway has a well-known biochemical role in cell-cycle regulation. It becomes overactive during the development of cancer, promoting cell proliferation and inhibiting apoptosis. Therefore, targeting this pathway has become important in the treatment of various malignant tumors. Selective inhibitors have been identified, but drugs that target multiple proteins within the pathway have shown higher efficacy and limited drug resistance, making them promising anticancer agents. This survey focuses on small molecule drugs capable of modulating the PI3K/PKB/mTOR signaling pathway as potential pharmacological treatments for cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Marina Ferreira Candido, Mariana Medeiros, Luciana Chain Veronez, David Bastos, Karla Laissa Oliveira, Julia Alejandra Pezuk, Elvis Terci Valera, Maria Sol Brassesco
Summary: Childhood cancer is rare but has a high mortality rate, with one child dying of cancer every 3 minutes. In this study, the expression patterns of a selected group of kinases in pediatric solid tumors were analyzed, and their correlation with clinical outcomes was evaluated. Additionally, the vulnerability of different cancer cell lines to kinase inhibition and the availability of kinase-targeted compounds for pediatric tumors were investigated. The study also discussed the challenges in translating these findings into clinical options.
Review
Chemistry, Medicinal
Jingyu Zhang, Yu Zhang, Bingxue Qu, Haiyan Yang, Shengquan Hu, Xiaowu Dong
Summary: Anti-cancer immunotherapy, including cellular immunotherapy, immune checkpoint inhibitors, and cancer vaccines, has revolutionized the treatment of various malignancies in recent decades. The focus has shifted towards developing small molecule inhibitors to overcome the limitations of monoclonal antibodies. Clinical trials are currently testing the combination of immune checkpoint inhibitors with various small molecule agonists/inhibitors to improve treatment outcomes and prevent tumor recurrence.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Zhiwei Ma, Sheng-You Huang, Fei Cheng, Xiaoqin Zou
Summary: Efficient ensemble docking algorithm is applied to dock ligands against multiple protein targets simultaneously. Using protein kinases as an example, the algorithm is shown to be effective in screening for inhibitors and investigating their selectivities for multiple target proteins.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Multidisciplinary Sciences
Zhiyang Zhou, Bi Peng, Juanni Li, Kewa Gao, Yuan Cai, Zhijie Xu, Yuanliang Yan
Summary: Alterations in MEK1 vary among different types of cancer, with distinct clinical implications on patient prognosis. This study provides a comprehensive analysis of MEK1 alterations and clinical significance, highlighting the importance of personalized therapy strategies based on MEK1 status in cancer treatment.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Margherita Turinetto, Anna A. Valsecchi, Valentina Tuninetti, Giulia Scotto, Fulvio Borella, Giorgio Valabrega
Summary: The prognosis of invasive cervical cancer remains poor and the standard treatment approach has not made significant progress. However, recent research on the interaction between the disease and the immune system has opened up new possibilities for immune therapy. Immunotherapy strategies such as immune checkpoint inhibitors, tumor infiltrating lymphocytes, and antibody drug conjugates have shown promising results in clinical trials. The development of predictive biomarkers is also being explored to guide treatment decisions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
