Microtubules are among the most studied and best characterized cancer targets identified to date. Many microtubule stabilizers have been introduced so far that work by disrupting the...
Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue
Prostate cancer (PC) is both an age- and an androgen-dependent disease. Paradoxically, systemic levels of androgens decline with age as the risk of PC rises. While there is no...
Physicochemical and biopharmaceutical properties
This webinar describes our modeling methodology and highlights the performance of key models. Special attention is devoted to our novel method of predicting macroscopic pKa, and our "Absorption Risk" Score.
It’s like playing with a better tennis partner
Are you a whistle-blower? Or do you cringe just to read those words? According to Margaret Heffernan* (links to a dead link) in a 2012 TEDTalk, most whistle-blowers are good guys. A whistle-blower can provide constructive conflict, which is vital for success. Heffernan says that great research teams, relationships, and businesses allow people to deeply disagree. When we are afraid of conflict, our doubts remain hidden. But when we dare to break that silence – when we dare to create conflict – we enable ourselves and the people around us to do our very best thinking.
Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer
The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of...
Simulations Plus Signs Material Transfer Agreement with National Institute of Environmental Health Sciences
Software Programs Will Help Prioritize Testing for the National Toxicology Program
A population pharmacokinetic and pharmacodynamic analysis of peginesatide in patients with chronic kidney disease on dialysis
Peginesatide (OMONTYS®) is an erythropoiesis-stimulating agent that was indicated in the United States for the treatment of anemia due to chronic kidney disease in adult patients on dialysis prior to...
Intelligent Wondering 8211 Investigative Clinical Pharmacology
Reviews of new drug applications by regulatory authorities worldwide grow ever more rigorous. I think that one reason for this heightened scrutiny is that reviewers have, over the last 10 years, read many submissions containing results of pharmacometric modeling and simulation analyses. With the use of modeling, explorations of the determinants of drug efficacy and safety are more thorough, and the analyses provide solid support for dose recommendations and labeling content. In short, I think that model-based analyses have raised reviewers’ expectations.
Simulations Plus Reports Preliminary Revenues for Third Fiscal Quarter FY2013
Preliminary Revenues Increased 11.7% for New Record Third Quarter
Compartmental absorption modeling and site of absorption studies to determine feasibility of an extended-release formulation of an HIV-1 attachment inhibitor phosphate ester prodrug
BMS-663068 is a phosphonooxymethyl ester prodrug under development for the treatment of HIV/AIDS. The prodrug is designed to overcome the solubility-limited bioavailability of the active moiety, BMS-626529.
Application of Target-Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors
Replacement of hydrogen with fluorine within three pairs of structurally similar small molecule inhibitors of heat shock protein 90 (HSP90) resulted in differences in inhibition constants (K(i)) in vitro as well...
In silico modeling to predict drug-induced phospholipidosis
Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review.
Simulations Plus Releases ADMET Predictor™ 6.5
Software Upgrade Increases Number of Predictive Models, Adds User Convenience Features
Get over it!
Brené Brown is a researcher at the University of Houston who studies vulnerability, courage, authenticity, and shame.* She speaks to many different audiences, including corporations and universities. Often, the person arranging a presentation timidly suggests that it might be better if she does not mention vulnerability or shame in her presentation. When asked what they want to hear about, the reply is “innovation, creativity, and change.” Her emphatic retort is that, “vulnerability is the birthplace of innovation, creativity and change!” To learn more, watch her second TEDTalk, Listening to Shame, here:
Reduction in Interindividual Variability and Clinical Significance Ratio in Covariate Assessment
Covariate analysis has become a customary and expected part of population pharmacokinetic (PK) and pharmacokinetic/ pharmacodynamic (PK/PD) modeling.1 The covariate submodel describes, explains, and…
Simulations Plus Software Used in Regulatory Submittals
US FDA, UK MHRA, and European EMA Accept Simulation Results in Applications
A Population PK Model for Cariprazine and the Metabolites
Cariprazine (CAR) is a potent dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors. Cariprazine was originally discovered by Gedeon Richter Plc. in Budapest, Hungary, and is…
Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin in Neonates and Infants
An amoxicillin PBPK model was previously developed and validated in healthy adults as well as adults with altered renal function [1-2]. The purpose of this study was to explore the utility of the model in...
Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor
GSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. GSK1322322 is active against community-acquired skin and respiratory...