Structural Determination of Three Different Series of Compounds as Hsp90 Inhibitors Using 3D-QSAR Modeling, Molecular Docking, and Molecular Dynamics Methods

Hsp90 is involved in correcting, folding, maturation and activation of a diverse array of client proteins; it has also been implicated in the treatment of cancer in recent years. In this work, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), molecular docking and molecular dynamics were performed on three different series of … Continued

Relationship Between AUC and Volume of Distribution

A few days ago on the pharmacokinetics listserve PharmPK, the following question appeared: I’m having trouble wrapping my head around this question from an online pharmacology quiz.  The question is “The larger the volume of distribution, the smaller the AUC of a given drug.”  The answer is given as “False.” As I look at the … Continued

Where Did the 80-125% Bioequivalence Criteria Come From?

Most people involved in clinical pharmacokinetics are familiar with the 80-125% criterion. This criterion is used to compare two treatments with the purpose of evaluating if the treatments are bioequivalent. But, where did this come from? Why 80-125%? Why not 90-110%? or why not 80-120%? Before we explain where 80-125% came from, let me explain … Continued

Deciding on Which Drug-drug Interactions to Evaluate in the Clinic

Drug-drug interactions are a critical research area in pharmaceutical drug development. One of the most tragic examples of drug-drug interactions was the antihistamine terfenadine. Terfenadine (also known as Seldane) was a common antihistamine intended to block the effects of an allergic rhinitis. Upon administration terfenadine is metabolized to fexofenadine by the cytochrome P450 3A4 isoform. … Continued

Generics and Bioequivalence

As the debate about health care in the United States continues forward, the term “generic drugs” has become rather commonplace. What are generic drugs? Are they safe to use? Why do we have them? And what is bioequivalence? All of these are common questions that I hope to answer with my post today. What are … Continued

What are Compartmental Models?

Almost everyone familiar with pharmaceuticals has heard a conversation like this before: Scientist 1: “What are the pharmacokinetics of Drug X?” Scientist 2: “Drug X follows a 1-compartment model in rats, but in monkeys it tends to have a distribution phase and seems to follow 2-compartment kinetics.” Scientist 1: Thinks to himself/herself …’What does a … Continued

What are Drug-drug Interactions Anyway?

A current buzz phrase in pharmaceutical research right now is “drug-drug interaction” or simply “drug interaction”. The definition of a drug-drug interaction has fluctuated over the last few years, not because of changes in research, but because of misconceptions in the research community. The US Food and Drug Administration (FDA) has published a draft guidance … Continued

Trial Designs—Non-inferiority vs. Superiority vs. Equivalence

The primary purpose of a clinical trial is to address a scientific hypothesis. To address a hypothesis, different statistical methods are used depending on the type of question to be answered. Most often the hypothesis is related to the effect of one treatment as compared to another. For example, one trial could compare the effectiveness … Continued

Molecular Modeling Studies on Imidazo[4,5-b]pyridine Derivatives as Aurora A Kinase Inhibitors Using 3D-QSAR and Docking Approaches

3D-QSAR and docking studies were performed on sixty imidazo[4,5-b]pyridine derivatives as Aurora A kinase inhibitors. The CoMFA and CoMSIA models using forthy-eight molecules in the training set, gave rcv2 values of 0.774 and 0.800, r2 values of 0.975 and 0.977, respectively. The external validation indicated that both CoMFA and CoMSIA models possessed high predictive powers … Continued

Insight into the Structural Requirements of Benzothiadiazine Scaffold-based Derivatives as Hepatitis C Virus NS5B Polymerase Inhibitors Using 3D-QSAR, Molecular Docking, and Molecular Dynamics

Hepatitis C virus (HCV) infection is a significant world health threat with frequently ineffective problem existed in the present treatment, thus representing a major unmet medical need. The nonstructural viral protein 5B (NS5B), one of the best-studied polymerase, has emerged as an attractive target for the development of novel therapeutics against hepatitis C virus. In … Continued