Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

Rationale: 4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC values against Aedes aegypti larvae.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling.

Recent Advancement in Breast Cancer Research: Insights from Model Organisms-Mouse Models to Zebrafish.

Animal models have been utilized for decades to investigate the causes of human diseases and provide platforms for testing novel therapies. Indeed, breakthrough advances in genetically engineered mouse (GEM) models and xenograft transplantation technologies have dramatically benefited in elucidating the mechanisms underlying the pathogenesis of multiple diseases, including cancer. The currently available GEM models have been employed to assess specific genetic changes that underlay many features of carcinogenesis, including variations in tumor cell proliferation, apoptosis, invasion, metastasis, angiogenesis, and drug resistance.

Bromodomain and extraterminal domain protein bromodomain inhibitor based cancer therapeutics.

Purpose Of Review: Bromodomain and extraterminal domain (BET) proteins are evolutionarily conserved, multifunctional super-regulators that specifically recognize acetyl-lysine on histones and other proteins controlling gene transcription. Several studies show that small molecules targeting these regulators preferentially suppress the transcription of cancer-promoting genes. Consequently, several BET inhibitors reached clinical trials and are in various stages for different kind of malignancies.

The Small Molecule BC-2059 Inhibits Wingless/Integrated (Wnt)-Dependent Gene Transcription in Cancer through Disruption of the Transducin -Like 1--Catenin Protein Complex.

The central role of -catenin in the Wnt pathway makes it an attractive therapeutic target for cancers driven by aberrant Wnt signaling. We recently developed a small-molecule inhibitor, BC-2059, that promotes apoptosis by disrupting the -catenin/transducin -like 1 (TBL1) complex through an unknown mechanism of action. In this study, we show that BC-2059 directly interacts with high affinity for TBL1 when in complex with -catenin.