This report describes development of an in silico, expert rule-based method for the classification of chemicals into irritants or non-irritants to eye, as defined by the Draize test.
Discovery of a Potent, Orally Available Dual CysLT1 and CysLT2 Antagonist with Dicarboxylic Acid
A potent, orally available dual CysLT1 and CysLT2 receptor antagonist with a dicarboxylic acid is described. 4-(3-(Carboxymethyl)-4-{(E)-2-[4-(4-phenoxybutoxy)phenyl]vinyl}-1H-indol-1-yl)butanoic acid...
Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem
Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms.
In silico prediction of hERG inhibition
The voltage-gated potassium channel encoded by hERG carries a delayed rectifying potassium current (IKr) underlying repolarization of the cardiac action potential.
Elucidation of the Multiple Activities of Abiraterone by a Synthetic Chemistry Approach
Objective: Novel agents to treat metastatic prostate cancer include a class of drugs which function primarily by inhibiting the action of the CYP17 enzyme, which results...
The importance of critical micellar concentration for the prediction of solubility enhancement in biorelevant media
This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF).
In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a ‘parallel progression approach to drug design’ applied to ß-blockers
The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development.
Phenotypic and molecular characterization of circulating tumor cells (CTCs) in patients with castration resistant prostate cancer (CRPC) undergoing treatment with abiraterone acetate or enzalutamide
Despite the introduction of a number of new treatment options (such as abiraterone acetate and enzalutamide) for castration resistant prostate cancer (CRPC), patients with...
Warfarin-dependent gamma-carboxylation regulates androgen receptor activity
The anti-coagulant warfarin prevents the gamma-carboxylation (gla) of target proteins by interfering with the vitamin K cycle through its inhibition of the vitamin K...
Understanding Disease-Drug Interactions in Cancer Patients: Implications for Dosing Within the Therapeutic Window
The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters.
The influence of salt chaotropicity, column hydrophobicity and analytes’ molecular properties on the retention of pramipexole and its impurities
The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of...
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model
The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in...
Design, Synthesis and Pharmacological evaluation of N-[4-(4-(alkyl/aryl/heteroaryl) -piperazin-1-yl) -phenyl] -carbamic acid ethyl ester derivatives as novel anticonvulsant agents
A series of alkyl/aryl/heteroaryl piperazine derivatives (37–54) were designed and synthesized as potential anticonvulsant agents. The target compounds are endowed with satisfactory physicochemical as well as pharmacokinetic properties.
Estimation of the chemical-induced eye injury using a weight-of-evidence (WoE) battery of 21 artificial neural network (ANN) c-QSAR models (QSAR-21): Part I: Irritation potential
Evaluation of potential chemical-induced eye injury through irritation and corrosion is required to ensure occupational and consumer safety for industrial, household and cosmetic ingredient chemicals.
Application of Absorption Modeling to Predict Bioequivalence Outcome of Two Batches of Etoricoxib Tablets
As part of the overall product development and manufacturing strategy, pharmaceutical companies routinely change formulation and manufacturing site.
Prediction of blood-brain barrier permeation of a-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis
Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (IRs).
Interspecies prediction of oral pharmacokinetics of different formulations from dogs to human: physiologically based pharmacokinetic modelling combined with biorelevant dissolution
The aim of the present study was to use physiologically based pharmacokinetic (PBPK) modelling combined with biorelevant dissolution to quantitatively predict dog oral drug pharmacokinetic (PK)...
Evaluation and comparison of benchmark QSAR models to predict a relevant REACH endpoint: The bioconcentration factor (BCF)
The bioconcentration factor (BCF) is an important bioaccumulation hazard assessment metric in many regulatory contexts. Its assessment is required by the REACH regulation...
Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug
In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting a substantial fraction of patients.
Computational Prediction of Drug Solubility in Fasted Simulated and Aspirated Human Intestinal Fluid
To develop predictive models of apparent solubility (Sapp) of lipophilic drugs in fasted state simulated intestinal fluid (FaSSIF) and aspirated human intestinal fluid (HIF).