Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination

…, C Rotter, HR Miller, G Chang, SJ Steyn… - Journal of medicinal …, 2010 - ACS Publications
Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall
elimination (Fg), and fraction escaping hepatic elimination (Fh). In this study, using a database …

Predicting clearance mechanism in drug discovery: extended clearance classification system (ECCS)

MV Varma, SJ Steyn, C Allerton, AF El-Kattan - Pharmaceutical research, 2015 - Springer
Early prediction of clearance mechanisms allows for the rapid progression of drug discovery
and development programs, and facilitates risk assessment of the pharmacokinetic …

[HTML][HTML] Leucine-rich repeat kinase 2 (LRRK2) pharmacological inhibition abates α-synuclein gene-induced neurodegeneration

…, KB Fraser, E Needle, Y Chen, SJ Steyn… - Journal of Biological …, 2015 - ASBMB
Therapeutic approaches to slow or block the progression of Parkinson disease (PD) do not
exist. Genetic and biochemical studies implicate α-synuclein and leucine-rich repeat kinase 2 …

Discovery and Preclinical Profiling of 3-[4-(Morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant …

…, Y Chen, E Needle, Z Berger, SJ Steyn… - Journal of medicinal …, 2015 - ACS Publications
Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson’s disease (PD)
by genome-wide association studies (GWAS). The most common LRRK2 mutation, …

pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery

MV Varma, I Gardner, SJ Steyn, P Nkansah… - Molecular …, 2012 - ACS Publications
The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a
basis for predicting the oral absorption of drugs. These concepts have been extended in the …

Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1H)-one Series of Potent d-Amino Acid Oxidase (DAAO) Inhibitors

…, SM Sakya, S Sheehan, SJ Steyn… - Journal of medicinal …, 2009 - ACS Publications
3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional
assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a …

Discovery of the Potent and Selective M1 PAM-Agonist N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine-2 …

…, V Reinhart, R Salomon-Ferrer, SJ Steyn… - Journal of medicinal …, 2016 - ACS Publications
It is hypothesized that selective muscarinic M 1 subtype activation could be a strategy to
provide cognitive benefits to schizophrenia and Alzheimer’s disease patients while minimizing …

A perspective on the prediction of drug pharmacokinetics and disposition in drug research and development

L Di, B Feng, TC Goosen, Y Lai, SJ Steyn… - Drug metabolism and …, 2013 - ASPET
Prediction of human pharmacokinetics of new drugs, as well as other disposition attributes,
has become a routine practice in drug research and development. Prior to the 1990s, drug …

Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor

…, LR Pustilnik, K Rafidi, S Ralston, AMK Rossi, SJ Steyn… - Cancer research, 2007 - AACR
Amplification and overexpression of erbB2 (Her-2/neu) proto-oncogene has been linked to
human malignancies including tumors of the breast, ovary, and stomach. It has been …

Imaging Leucine-Rich Repeat Kinase 2 In Vivo with 18F-Labeled Positron Emission Tomography Ligand

…, H Fu, T Shao, K Coffman, SJ Steyn… - Journal of Medicinal …, 2022 - ACS Publications
Leucine-rich repeat kinase 2 (LRRK2) has been demonstrated to be closely involved in the
pathogenesis of Parkinson’s disease (PD), and pharmacological blockade of LRRK2 …