Article
Pharmacology & Pharmacy
Rehab A. Alshammari, Fadilah S. Aleanizy, Amal Aldarwesh, Fulwah Y. Alqahtani, Wael A. Mahdi, Bushra Alquadeib, Qamraa H. Alqahtani, Nazrul Haq, Faiyaz Shakeel, Hosam G. Abdelhady, Ibrahim A. Alsarra
Summary: This study developed RBX nanoparticles using PAMAM dendrimers for the treatment of diabetic retinopathy, providing a safe and effective method for RBX administration. The drug loading efficiency and in vitro release of the RBX:PAMAM dendrimer complexes were evaluated, and the 5:1 complex showed the highest loading efficiency and drug release. The nanoformulation improved the therapeutic outcomes of anti-VEGF therapy and the bioavailability of RBX for preventing vision loss in patients with diabetic retinopathy.
Article
Pharmacology & Pharmacy
Yao Chen, Bernardo L. Sabatini
Summary: In addition to inhibiting PKA activity, PKI was found to facilitate the activation of multiple isoforms of PKC at higher concentrations. This suggests the need for appropriate interpretation of experimental results when using PKI as a pharmaceutical agent. The study provides a foundation for exploring the potential functions of PKI in regulating PKC activity and coordinating PKC and PKA activities.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Sona Krajcovicova, Radek Jorda, David Vanda, Miroslav Soural, Vladimir Krystof
Summary: An efficient synthetic approach for trisubstituted imidazo [4,5-c]pyridines as BTK inhibitors was reported, with high tolerance of C6 substitutions observed. Cellular experiments indicated selective BTK targeting, suggesting the inhibitors could be potential options after ibrutinib failure.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Jin Ma, Jiang Ren, Midory Thorikay, Maarten van Dinther, Gonzalo Sanchez-Duffhues, Josselin Caradec, Pascal Benderitter, Jan Hoflack, Peter ten Dijke
Summary: Novel macrocyclic compounds OD16 and OD29 have been synthesized as inhibitors of BMP type I receptor and VEGF-induced signaling, demonstrating potential as anti-angiogenesis therapeutic agents by impairing endothelial cell function and inhibiting angiogenesis in both normal and tumour-induced conditions in vitro and in zebrafish embryos. These compounds show promise for overcoming therapy resistance and improving clinical efficacy in targeting angiogenesis pathways.
Article
Multidisciplinary Sciences
Damian Emilio Berardi, Lizeth Ariza Bareno, Natalia Amigo, Luciana Canonero, Maria de las Nieves Pelagatti, Andrea Nora Motter, Maria Agustina Taruselli, Maria Ines Diaz Bessone, Stefano Martin Cirigliano, Alexis Edelstein, Maria Giselle Peters, Miriam Diament, Alejandro Jorge Urtreger, Laura Beatriz Todaro
Summary: In the treatment of breast cancer, the combination of all-trans-retinoic acid (ATRA) and the classical PCK inhibitor Go6976 significantly reduces tumor proliferative potential and increases apoptosis rate, promoting an anti-oncogenic profile. Additionally, the combined treatment reduces the growth, self-renewal, and clonogenicity of cancer stem cells, leading to decreased tumor growth, metastatic spread, and cancer stem cells frequency.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Hematology
Jan A. Burger
Summary: The study reveals that MARCKS protein is differentially expressed in patients with chronic lymphocytic leukemia based on the mutation status of IGHV, and its expression and phosphorylation are linked to CLL cell migration through key signaling pathways. The findings were also confirmed in samples from patients treated with the BTK inhibitor acalabrutinib.
Article
Chemistry, Medicinal
Seungbeom Lee, Jisu Kim, Jeyun Jo, Jae Won Chang, Jaehoon Sim, Hwayoung Yun
Summary: Bivalent kinase inhibitors have emerged as a promising approach for targeting specific kinases with enhanced selectivity and affinity through increased interactions with target enzymes. Recent developments have led to the creation of bivalent compounds with high kinase affinity, biological and chemical stability in vivo, offering significant potential for therapeutic applications. This review provides a comprehensive overview of hetero-bivalent kinase inhibitors and discusses their advantages, limitations, and future prospects compared to monovalent kinase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Takahito Kawano, Junichi Inokuchi, Masatoshi Eto, Masaharu Murata, Jeong-Hun Kang
Summary: PKC is a family of important kinases classified into three subfamilies based on structural and activation characteristics, and used for understanding intracellular signaling pathways and treating related diseases. While PKC inhibitors in clinical trials for cancers did not show significant benefits, there is still potential for their application in research on other diseases.
Review
Oncology
Emmy D. G. Fleuren, Myrella Vlenterie, Winette T. A. van der Graaf
Summary: Osteosarcoma (OS) and Ewing sarcoma (ES) are two common types of primary bone cancer that mainly affect young people. Despite aggressive treatment, survival rates have not significantly improved in the past four decades. Clinical efficacy has been observed with some mono-Receptor Tyrosine Kinase (RTK) inhibitors, but only in small subsets of patients. Newer generation multi-RTK inhibitors have shown efficacy in larger groups of OS or ES patients. However, registration for these indications has not been obtained, making it difficult to implement these drugs in routine patient care.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bader Huwaimel, Sravan Jonnalagadda, Shirisha Jonnalagadda, Fatema T. Zahra, Alessio Nocentini, Claudiu T. Supuran, Constantinos M. Mikelis, Paul C. Trippier
Summary: Angiogenesis inhibitors, such as chlorinated benzothiadiazines, have been found to suppress VEGF-induced endothelial cell proliferation by inhibiting VEGFR2 phosphorylation. These inhibitors show selectivity and lack cytotoxicity against various cell lines. Compound 17b, in particular, demonstrates high selectivity and potential as a novel angiogenesis inhibitor for further development.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Anupreet Kharbanda, Lingtian Zhang, Debasmita Saha, Phuc Tran, Ke Xu, Ming O. Li, Yuet-Kin Leung, Brendan Frett, Hong-yu Li
Summary: TGF beta plays a crucial role in maintaining the homeostasis of epithelial and neural tissues, wound repair, and immune responses. Dysregulation of TGF beta is associated with various diseases, with modifying the tumor microenvironment being of significant clinical interest. Despite efforts, there is currently no FDA-approved therapy to inhibit the TGF beta pathway, but targeting TGF beta RI kinase remains a major approach.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Seyed-Omar Zaraei, Nour N. Al-Ach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Rimas T. Tokatly, Rawan R. Kalla, Mouna A. Munther, Marwa M. Wahba, Aya M. Alshihabi, Mahmoud K. Shehata, Rawan M. Sbenati, Afnan I. Shahin, Raafat El-Awady, Taleb H. Al-Tel, Mohammed I. El-Gamal
Summary: This article presents the design, synthesis, and biological screening results of a new series of diarylurea and diarylamide derivatives with a quinoline core armed with dimethylamino or morpholino side chains. The compounds showed broad-spectrum antiproliferative activity against a panel of 60 cancer cell lines, with three of them demonstrating higher potency than the reference drug, sorafenib. The compounds also exhibited high selectivity for C-RAF kinase, making them potential inhibitors for this molecular target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Haixiang Zhang, Yinan Zheng, Lifang Hou, Cheng Zheng, Lei Liu
Summary: In this study, a novel method is introduced to identify potential mediators in high-dimensional Cox regression, with successful control of false discovery rate through data dimension reduction and multiple-testing procedure. Application to DNA methylation markers in lung cancer patients reveals two potential mediating epigenetic markers.
Review
Biochemistry & Molecular Biology
Hyunwook Cho, Jung-Mi Hah
Summary: JNK3 plays a crucial role in neurodegenerative diseases, and this study summarizes the research on JNK3 inhibitors, focusing on structural and docking insights.
Article
Chemistry, Multidisciplinary
Sergiy A. Starosyla, Galyna P. Volynets, Mykola Protopopov, Volodymyr G. Bdzhola, Denis O. Pashevin, Valentyna O. Polishchuk, Taisiia O. Kozak, Dmytro O. Stroi, Victor E. Dosenko, Sergiy M. Yarmoluk
Summary: In this article, ligand-based PKC beta pharmacophore models were developed and validated for identifying novel potent PKC beta inhibitors. Molecular docking and virtual screening were performed to select 28 top-scored compounds for further biological research.
STRUCTURAL CHEMISTRY
(2023)
