Alectinib, a lipophilic, basic, anaplastic lymphoma kinase (ALK) inhibitor with very low aqueous solubility, has received Food and Drug Administration-accelerated approval for the...
A Physiologically Based Pharmacokinetic Model for Ganciclovir and Its Prodrug Valganciclovir in Adults and Children
A physiologically based pharmacokinetic (PBPK) model has been developed for ganciclovir and its prodrug valganciclovir.
Simulations Plus Reports Third Quarter FY2016 Financial Results
Record quarterly revenue, 9moFY16 diluted EPS increased 23% to a record $0.242 from $0.196
The spring alpha-helix coordinates multiple modes of HCV NS3 helicase action
Genomic DNA replication requires helicases to processively unwind duplexes.
Simulations Plus Sets Date for 3rd Quarter 2016 Earnings Release and Conference Call
Conference Call to be on Thursday, July 14, at 4:15 PM ET
A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats
We compared the model performance of two semi-mechanistic pharmacokinetic-pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model...
Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kß Inhibitors.
A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized.
Discovery of a Potential HER2 Inhibitor from Natural Products for the Treatment of HER2-Positive Breast Cancer.
Breast cancer is one of the most lethal types of cancer in women worldwide due to the late stage detection and resistance to traditional chemotherapy.
Integration of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models with Adverse Outcome Pathways (AOPs) and Environmental Exposure Models to Screen for Environmental Hazards
A computational framework was developed to assist in screening and prioritizing chemicals based on their dosimetry, toxicity, and potential exposures.
Physiologically-Based Pharmacokinetic Modeling in Pediatric Oncology Drug Development
Childhood cancer represents more than 100 rare and ultra-rare diseases, with an estimated 12,400 new cases diagnosed each year in the United States.
Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels
The emergence of genetic data linking Nav1.7 sodium channel over- and under- expression to human pain signalling has led to an interest in the treatment of chronic pain through inhibition of Nav1.7 channels.
Descriptors and their selection methods in QSAR analysis: paradigm for drug design
The screening of chemical libraries with traditional methods, such as high-throughput screening (HTS), is expensive and time consuming.
Modeling ADMET
Drug discovery and development is a costly and time-consuming endeavor (Calcoen et al. Nat Rev Drug Discov 14(3):161–162, 2015; The truly staggering cost of inventing new drugs
In Silico Models for Acute Systemic Toxicity
In this chapter, we give an overview of the regulatory requirements for acute systemic toxicity information in the European Union, and we review the availability of structure-based computational models...
In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results
Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals.
Quantitative Estimation Of Predictive Uncertainty
The performance of QSAR models has traditionally been evaluated in terms of aggregate statistics – sensitivity, specificity, root mean square error (RMSE), R2, etc. – for some kind of test set.
Design, Synthesis, and Biological Evaluation of Novel PARP-1 Inhibitors Based on a 1H-Thieno[3,4-d] Imidazole-4-Carboxamide Scaffold
A series of poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing a novel scaffold, the 1H-thieno[3,4-d]imidazole-4-carboxamide moiety, was designed and synthesized.
Physiologically based pharmacokinetic (PBPK) model for intramuscular injection of aripiprazole
Aripiprazole is an atypical antipsychotics drug that is widely used in the treatment of agitation associated with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder.
Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines
In a previous communication we reported on the discovery of aminopyridine 1as a potent, selective and orally active S1P1 receptor agonist.