The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects...
Similarity-based virtual screening for microtubule stabilizers reveals novel antimitotic scaffold
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...
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...
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...
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.
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...
Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides
Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug...
Clinical Pharmacokinetics of Buffered Propranolol Sublingual Tablet (Promptol™)—Application of a New “Physiologically Based” Model to Assess Absorption and Disposition
Sublingual administration of certain buffered propranolol may improve the rate and extent of absorption compared to oral administration.
Docking and in silico ADMET studies of noraristeromycin, curcumin and its derivatives with Plasmodium falciparum SAH hydrolase: A molecular drug target against malaria
The Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (pfSAHH) enzyme has been considered as a potential chemotherapeutic target against malaria due to the amino acid differences...
Interactions of laulimalide, peloruside, and their derivatives with the isoforms of ß-tubulin
Interactions of laulimalide, peloruside, and their derivatives with the isoforms of β-tubulin.
Predicting Pharmacokinetic Profiles Using In Silico Derived Parameters
Human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential clinical candidates where the accurate estimation of clearance, volume of distribution, bioavailability...
In vitro to in vivo extrapolation and physiologically based modeling of cytochrome P450 mediated metabolism in beagle dog gut wall and liver
The beagle dog is a widely used in vivo model to guide clinical formulation development and to explore the potential for food effects.
Mechanistic Investigation of Negative Food Effect for BCS Class III Compounds in Solid Dosage Forms
Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release.
Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug using Lipophilic Fragments Disturbing the Crystal Lattice
Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility.
Predicting Pharmacokinetic Profiles Using in Silico Derived Parameters
Human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential clinical candidates where the accurate estimation of clearance, volume of distribution, bioavailability, and the plasma-concentration- time profiles are the desired end points.
Interaction of Silymarin Flavonolignans with Organic Anion Transporting Polypeptides (OATPs)
Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption...