Pharmacokinetics Profiler (PhaKinPro): Model Development, Validation, and Implementation as a Web Tool for Triaging Compounds with Undesired Pharmacokinetics Profiles.

Computational models that predict pharmacokinetic properties are critical to deprioritize drug candidates that emerge as hits in high-throughput screening campaigns. We collected, curated, and integrated a database of compounds tested in 12 major end points comprising over 10,000 unique molecules. We then employed these data to build and validate binary quantitative structure-activity relationship (QSAR) models.

Selene-Ethylenelacticamides and -Aryl-Propanamides as Broad-Spectrum Leishmanicidal Agents.

The World Health Organization classifies Leishmania as one of the 17 “neglected diseases” that burden tropical and sub-tropical climate regions with over half a million diagnosed cases each year. Despite this, currently available anti-leishmania drugs have high toxicity and the potential to be made obsolete by parasite drug resistance. We chose to analyze organoselenides for leishmanicidal potential given the reduced toxicity inherent to selenium and the displayed biological activity of organoselenides against Leishmania.

Integrated approach to elucidate metal-implant related adverse outcome pathways.

Exogenous metal particles and ions from implant devices are known to cause severe toxic events with symptoms ranging from adverse local tissue reactions to systemic toxicities, potentially leading to the development of cancers, heart conditions, and neurological disorders. Toxicity mechanisms, also known as Adverse Outcome Pathways (AOPs), that explain these metal-induced toxicities are severely understudied. Therefore, we deployed in silico structure- and knowledge-based approaches to identify proteome-level perturbations caused by metals and pathways that link these events to human diseases.

Allosteric Binders of ACE2 Are Promising Anti-SARS-CoV-2 Agents.

The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for acute treatment of the disease. We investigate whether compounds that bind the human angiotensin-converting enzyme 2 (ACE2) protein can decrease SARS-CoV-2 replication without impacting ACE2's natural enzymatic function.

Allosteric binders of ACE2 are promising anti-SARS-CoV-2 agents.

The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for an acute treatment for the disease. We investigate whether compounds that bind the human ACE2 protein can interrupt SARS-CoV-2 replication without damaging ACE2’s natural enzymatic function.

Simplex representation of molecular structure as universal QSAR/QSPR tool.

We review the development and application of the Simplex approach for the solution of various QSAR/QSPR problems. The general concept of the simplex method and its varieties are described. The advantages of utilizing this methodology, especially for the interpretation of QSAR/QSPR models, are presented in comparison to other fragmentary methods of molecular structure representation.