A5068550720- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- Lipoproteins and Cardiovascular Health
- High-Temperature Coating Behaviors
- Cholesterol and Lipid Metabolism
- Analytical Chemistry and Chromatography
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Metabolomics and Mass Spectrometry Studies
- Liver Disease Diagnosis and Treatment
- Advanced ceramic materials synthesis
- Advanced materials and composites
- Metal complexes synthesis and properties
- Cancer, Lipids, and Metabolism
- Machine Learning in Materials Science
- Metal and Thin Film Mechanics
- Wnt/β-catenin signaling in development and cancer
- Power Systems and Renewable Energy
- Catalytic Processes in Materials Science
- Biochemical and Molecular Research
- Pharmacological Effects and Toxicity Studies
- Oil and Gas Production Techniques
- Lipid metabolism and disorders
- Nuclear Materials and Properties
- Plant biochemistry and biosynthesis
Pfizer (United States)
2013-2024
University of Toledo
2021-2023
ON Semiconductor (United States)
2020
Foton Motors (China)
2017
SUNY Downstate Health Sciences University
2009
The Ohio State University
1993
New Jersey Institute of Technology
1991
University of Kansas
1988
Cleveland State University
1981-1987
United States Department of Energy
1978
Abstract An integrated molecular modeling system for designing and studying organic bioorganic molecules their complexes using mechanics is described. The graphically controlled, atom‐based allows the construction, display manipulation of having as many 10,000 atoms provides interactive, state‐of‐the‐art on any subset up to 1,000 atoms. semiautomates graphical construction analysis complex structures ranging from polycyclic biopolymers mixed complexes. We have placed emphasis providing...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn internal-coordinate Monte Carlo method for searching conformational spaceGeorge Chang, Wayne C. Guida, and W. Clark StillCite this: J. Am. Chem. Soc. 1989, 111, 12, 4379–4386Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/ja00194a035https://doi.org/10.1021/ja00194a035research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformations of cycloheptadecane. A comparison methods for conformational searchingMartin Saunders, K. N. Houk, Yun Dong Wu, W. Clark Still, Mark Lipton, George Chang, and Wayne C. GuidaCite this: J. Am. Chem. Soc. 1990, 112, 4, 1419–1427Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February...
Oral bioavailability (F) is a product of fraction absorbed (Fa), escaping gut-wall elimination (Fg), and hepatic (Fh). In this study, using database comprised Fa, Fg, Fh, F values for 309 drugs in humans, an analysis the interrelation physicochemical properties individual parameters was carried out order to define space optimum human oral bioavailability. Trend clearly indicated molecular weight (MW), ionization state, lipophilicity, polar descriptors, free rotatable bonds (RB) influence...
Species independence of brain tissue binding was assessed with a large number structurally diverse compounds using equilibrium dialysis homogenates seven species and strains (Wistar Han rat, Sprague-Dawley CD-1 mouse, Hartley guinea pig, beagle dog, cynomolgus monkey, human). The results showed that the fractions unbound were strongly correlated correlation coefficients ranging from 0.93 to 0.99. cross-species/strain correlations not significantly different interassay same species. linear...
A microsomal triglyceride transfer protein (MTP) inhibitor, CP-346086, was identified that inhibited both human and rodent MTP activity [concentration giving half-maximal inhibition (IC50) 2.0 nM]. In Hep-G2 cells, CP-346086 apolipoprotein B (apoB) secretion (IC50 2.6 nM) without affecting apoA-I or lipid synthesis. When administered orally to rats mice, lowered plasma triglycerides [dose 30% lowering (ED30) 1.3 mg/kg] 2 h after a single dose. Coadministration with Tyloxapol demonstrated due...
Abstract Glycogen synthase kinase‐3 (GSK‐3) regulates multiple cellular processes in diabetes, oncology, and neurology. N ‐(3‐(1H‐1,2,4‐triazol‐1‐yl)propyl)‐5‐(3‐chloro‐4‐methoxyphenyl)oxazole‐4‐carboxamide (PF‐04802367 or PF‐367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK‐3 to date. Its efficacy was demonstrated modulation tau phosphorylation vitro vivo. Whereas kinetics PF‐367 binding brain tissues are too fast for an effective...
Biliary excretion (BE) is a major elimination pathway, and its prediction particularly important for optimization of systemic and/or target-site exposure new molecular entities. The objective to characterize the physicochemical space associated with hepatobiliary transport rat BE develop in silico models. 123 in-house compounds was obtained using bile-duct cannulated model. Human hepatic uptake transporters (hOATP1B1, hOATP1B3, hOATP2B1, rOatp1b2) substrates (<i>n</i> = 183) were identified...
Accurate prediction of human pharmacokinetics (PK) remains one the key objectives drug metabolism and PK (DMPK) scientists in discovery projects. This is typically performed by using vitro-in vivo extrapolation (IVIVE) based on mechanistic models. In recent years, machine learning (ML), with its ability to harness patterns from previous outcomes predict future events, has gained increased popularity application absorption, distribution, metabolism, excretion (ADME) sciences. study compares...
Fraction unbound (<i>f</i><sub>u</sub>) of liver tissue, hepatocytes, and other cell types is an essential parameter used to estimate drug concentration intracellular free concentration. <i>f</i><sub>u,liver</sub> <i>f</i><sub>u,cell</sub> are frequently measured in multiple species discovery development for various applications. A comparison study 12 matrices hepatocytes five different (mouse, rat, dog, monkey, human), as well Huh7 human embryonic kidney 293 lines, was conducted 22...
Apparent intrinsic clearance (CLia) determined from microsomal stability assays is a cornerstone in drug discovery. Categorical bins are routinely applied to this end point facilitate analysis. However, such ignore the interdependent nature of apparent microsome on several ADME parameters. Considering CLia as determinant for both metabolic and potential dose more appropriate. In context with proper accounting nonspecific binding microsomes plasma, consideration compounds higher may be...
The fraction unbound in the incubation, fu,inc, is an important parameter to consider evaluation of intrinsic clearance measurements performed vitro hepatocytes or microsomes. Reliable estimates fu,inc based on a compound's structure have potential positively impact screening timelines drug discovery. Previous works suggested that primarily driven by passive processes and can be described using physicochemical properties such as lipophilicity protonation state molecule. While models these...