A KNIME Workflow to Assist the Analogue Identification for Read-Across, Applied to Aromatase Activity.

The reduction and replacement of in vivo tests have become crucial in terms of resources and animal benefits. The read-across approach reduces the number of substances to be tested, exploiting existing experimental data to predict the properties of untested substances. Currently, several tools have been developed to perform read-across, but other approaches, such as computational workflows, can offer a more flexible and less prescriptive approach.

Exploration of structural requirements for azole chemicals towards human aromatase CYP19A1 activity: Classification modeling, structure-activity relationships and read-across study.

Human aromatase, also called CYP19A1, plays a major role in the conversion of androgens into estrogens. Inhibition of aromatase is an important target for estrogen receptor (ER)-responsive breast cancer therapy. Use of azole compounds as aromatase inhibitors is widespread despite their low selectivity.

Skin sensitization quantitative QSAR models based on mechanistic structural alerts.

Allergic contact dermatitis is increasingly of interest for the hazard characterization of chemicals. in vivo animal testing is usually adopted but in silico approaches are becoming the new frontier due to their swiftness and economic efficiency. Indeed, in silico models can rationalise the experimental outcomes besides having predictive ability.

Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies.

The ABCB1 transporter also known as P-glycoprotein (P-gp) is a transmembrane protein belonging to the ATP binding cassette super-family of transporters; it is a xenobiotic efflux pump that limits intracellular drug accumulation by pumping the compounds out of cells. P-gp contributes to a decrease of toxicity and possesses broad substrate specificity. It is involved in the failure of numerous anticancer and antiviral chemotherapies due to the multidrug resistance (MDR) phenomenon, where it removes the chemotherapeutics out of the targeted cells.

Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis.

Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system.

Ensemble-Based Modeling of Chemical Compounds with Antimalarial Activity.

Background: Malaria or Paludism is a tropical disease caused by parasites of the Plasmodium genre and transmitted to humans through the bite of infected mosquitos of the Anopheles genre. This pathology is considered one of the first causes of death in tropical countries and, despite several existing therapies, they have a high toxicity. Computational methods based on Quantitative Structure- Activity Relationship studies have been widely used in drug design work flows.