Genomic DNA replication requires helicases to processively unwind duplexes.
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.
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.
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.
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms
The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions.
In silico modeling of gastrointestinal drug absorption: predictive performance of three physiologically based absorption models
Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology.
The solubility-permeability interplay and oral drug formulation design: Two heads are better than one
Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect...
BDDCS, the Rule of 5 and drugability
The Rule of 5 methodology appears to be as useful today in defining drugability as when it was proposed, but recognizing that the database that we used includes only drugs that successfully reached the market.
Computational prediction of formulation strategies for beyond-rule-of-5 compounds
The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity.
Characterizing the Dissolution Profiles of Supersaturable Salts, Cocrystals, and Solvates to Enhance In Vivo Oral Absorption
The purposes of this study were to elucidate the type-specific characteristics of salt, cocrystal, and solvate formulations upon dissolution and precipitation, and to clarify their effect on enhancing oral absorption.
LC-ESI-MS/MS estimation of loratadine-loaded self-nanoemulsifying drug delivery systems in rat plasma: Pharmacokinetic evaluation and computer simulations by GastroPlus™
A rapid, sensitive, and accurate bioanalytical method was established for the quantitation and pharmacokinetic investigation of loratadine (LTD) in rat plasma by liquid chromatography–electrospray ionization...