Spectroscopic, biochemical and computational studies of bioactive DNA minor groove binders targeting 5'-WGWWCW-3' motif.

Spectroscopic, biochemical, and computational modelling studies have been used to assess the binding capability of a set of minor groove binding (MGB) ligands against the self-complementary DNA sequences 5'-d(CGCACTAGTGCG)-3' and 5'-d(CGCAGTACTGCG)-3'. The ligands were carefully designed to target the DNA response element, 5'-WGWWCW-3', the binding site for several nuclear receptors. Basic 1D H NMR spectra of the DNA samples prepared with three MGB ligands show subtle variations suggestive of how each ligand associates with the double helical structure of both DNA sequences.

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.

Introduction: Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients.

Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011-2020): Current Status and Future Prospects.

Pyrazole has been recognized as a pharmacologically important privileged scaffold whose derivatives produce almost all types of pharmacological activities and have attracted much attention in the last decades. Of the various pyrazole derivatives reported as potential therapeutic agents, this article focuses on pyrazole-based kinase inhibitors. Pyrazole-possessing kinase inhibitors play a crucial role in various disease areas, especially in many cancer types such as lymphoma, breast cancer, melanoma, cervical cancer, and others in addition to inflammation and neurodegenerative disorders.

A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors.

HER4 is a receptor tyrosine kinase that is required for the evolution of normal body systems such as cardiovascular, nervous, and endocrine systems, especially the mammary glands. It is activated through ligand binding and activates MAPKs and PI3K/AKT pathways. HER4 is commonly expressed in many human tissues, both adult and fetal.

Current status and future prospects of p38α/MAPK14 kinase and its inhibitors.

P38α (which is also named MAPK14) plays a pivotal role in initiating different disease states such as inflammatory disorders, neurodegenerative diseases, cardiovascular cases, and cancer. Inhibitors of p38α can be utilized for treatment of these diseases. In this article, we reviewed the structural and biological characteristics of p38α, its relationship to the fore-mentioned disease states, as well as the recently reported inhibitors and classified them according to their chemical structures.