This review covers literature describing research progress in erbB family tyrosine kinase inhibition over the last year. Excellent recent reviews are available, thus we have focussed on current developments of leading small molecule drug candidates as well as their erbB family inhibition profile. The most advanced erbB family tyrosine kinase (TK) inhibitors are demonstrating promising anti-cancer activity in clinical trials and are discussed. Several inhibition strategies are emerging: EGFR TK selective, irreversible TK inhibition and dual EGFR/erbB2 TK inhibitors. While small structural differences are seen in the leading compounds, the variations in their inhibition profiles and compound properties suggest that biological systems judge structural diversity differently. The readers' attention is drawn to common issues of selectivity and potency generally encountered with kinase inhibitors.
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http://dx.doi.org/10.2174/1568026023393309 | DOI Listing |
Cancer Med
February 2025
Pulmonology and Thoracic Oncology Department, APHP Hôpital Tenon and Sorbonne Université, Paris, France.
Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.
Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).
Pharmaceuticals (Basel)
January 2025
Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, Ukraine.
Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Centro de Química Médica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7780272, Chile.
Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure-activity relationship (QSAR) model to predict the inhibitory potency (pIC values) of FLT3 inhibitors, addressing the limitations of previous models in dataset size, diversity, and predictive accuracy. Using a dataset which was 14 times larger than those employed in prior studies (1350 compounds with 1269 molecular descriptors), we trained a random forest regressor, chosen due to its superior predictive performance and resistance to overfitting.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Clinical and Biological Sciences, University of Turin, 10124 Orbassano, Italy.
: Treatment with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has revolutionized disease management and has transformed CML from a life-threatening disease to a chronic condition for many patients. However, overcoming resistance, particularly related to leukemic stem cells (LSC) that can persist even when the bulk of the leukemic cells are eliminated, remains a significant challenge. : K562 and KU812 cell lines were treated in vitro with the TKI Imatinib (IM).
View Article and Find Full Text PDFMolecules
January 2025
Department of Chemistry, Technical University of Denmark, 206 Kemitorvet, 2800 Kgs Lyngby, Denmark.
A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.
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