A5011675722- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Wound Healing and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- Amino Acid Enzymes and Metabolism
- Pregnancy and preeclampsia studies
- Prenatal Screening and Diagnostics
- Fibroblast Growth Factor Research
- Angiogenesis and VEGF in Cancer
- Advanced Drug Delivery Systems
- Sphingolipid Metabolism and Signaling
- Peroxisome Proliferator-Activated Receptors
- Periodontal Regeneration and Treatments
- Gestational Diabetes Research and Management
- Sarcoma Diagnosis and Treatment
- Diabetes Treatment and Management
- Connective Tissue Growth Factor Research
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Renal Diseases and Glomerulopathies
- Biochemical and Molecular Research
- Hydrogels: synthesis, properties, applications
- Vascular Tumors and Angiosarcomas
- Venomous Animal Envenomation and Studies
- PI3K/AKT/mTOR signaling in cancer
AstraZeneca (United States)
2020-2025
AstraZeneca (United Kingdom)
2024
AbbVie (United States)
2024
University of Washington
1985-2020
Technische Hochschule Georg Agricola
2011
Niedersächsisches Landesgesundheitsamt
2011
Creighton University
2006
Bristol-Myers Squibb (United States)
1999
Ruhr University Bochum
1997-1998
BG University Hospital Bergmannsheil Bochum
1995-1998
The optimization of an allosteric fragment, discovered by differential scanning fluorimetry, to in vivo MAT2a tool inhibitor is discussed. structure-based drug discovery approach, aided relative binding free energy calculations, resulted AZ'9567 (21), a potent vitro with excellent preclinical pharmacokinetic properties. This showed selective antiproliferative effect on methylthioadenosine phosphorylase (MTAP) KO cells, both and vivo, providing further evidence support the utility inhibitors...
Growth factors are important substances in the central control of wound healing during exudative phase. Although these peptides have been applied frequently to chronic wounds clinical studies, little is known about naturally occurring levels at site correlation superficial wounds.We therefore investigated presence cytokines partial thickness wounds. In 16 patients undergoing reconstructive surgery, split-thickness skin were enclosed cutaneous vinyl chambers filled with 2.5 ml saline....
Metformin, an oral antihyperglycemic, is increasingly being prescribed to pregnant women with gestational diabetes. Metformin a hydrophilic cation and relies on organic transporters move across cell membranes. We previously demonstrated that human mouse placentas predominantly express transporter 3 (OCT3), but the impact of this maternal fetal disposition metformin unknown. Using immunofluorescence colocalization studies in term placenta, we showed OCT3 localized basal (fetal-facing)...
Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of the T cell receptor signaling pathway and therefore target interest for immunooncology. Nonselective HPK1 inhibitors may affect other components activation, blunting beneficial impact enhanced activity that results from inhibition itself. Here, we report discovery pyrazine carboxamide their optimization through structure-based drug design to afford highly selective inhibitor, compound 24 (AZ3246). This induces IL-2 secretion...
MAT2a is a methionine adenosyltransferase that synthesizes the essential metabolite S-adenosylmethionine (SAM) from and ATP. Tumors bearing co-deletion of p16 MTAP genes have been shown to be sensitive inhibition, making it an attractive target for treatment MTAP-deleted cancers. A fragment-based lead generation campaign identified weak but efficient hits binding in known allosteric site. By use structure-guided design systematic SAR exploration, were elaborated through merging growing...
Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in United States alone. A large portion methamphetamine and its metabolites eliminated by kidney renal clearance larger than glomerular filtration clearance. Yet mechanism active secretion poorly understood. The goals this study were to characterize interaction major organic cation transporters (OCTs) multidrug toxin extrusion (MATE) identify involved disposition metabolites, amphetamine...
Radiolabeled <i>meta</i>-iodobenzylguanidine (mIBG) is an important radiopharmaceutical used in the diagnosis and treatment of neuroendocrine cancers. mIBG known to enter tumor cells through norepinephrine transporter. Whole-body scintigraphy has shown rapid elimination kidney high accumulation several normal tissues, but underlying molecular mechanisms are unclear. Using transporter-expressing cell lines, we show that excellent substrate for human organic cation transporters 1–3 (hOCT1–3)...
OBJECTIVE: To evaluate the pharmacokinetics, safety, and tolerability of cefepime administered as an intravenous bolus short infusion. METHODS: A single-dose, pharmacokinetic study was conducted on 16 healthy men. Fifty milliliters a 40 mg/mL solution by continuous infusion in intervals three, five, 10, or 15 minutes. Blood sampled three minutes through 12 hours after end Analysis performed reverse-phase HPLC with ultraviolet detection. Cefepime plasma concentrations versus time were...
Methamphetamine is one of the most widely abused illicit drugs. Although human intoxication and multiple tissue toxicities frequently occur in abusers, little known about distribution methamphetamine or its primary metabolites, amphetamine <i>para</i>-hydroxymethamphetamine (<i>p</i>-OHMA), to their sites toxicity. This study determined pharmacokinetics, exposure, partition ratios major metabolites various mouse tissues investigated impact organic cation transporter 3 (Oct3) following i.v....
Background: Platelet‐derived growth factor (PDGF) has been used to promote healing in many vitro and vivo models of periodontal regeneration. PDGF interacts extensively with lysophosphatidic acid (LPA). We recently showed that LPA modulates the responses human gingival fibroblasts PDGF. The objectives this study were as follows: 1) evaluate basic interactions primary ligament (PDLFs) alone PDGF‐BB for promoting PDLF migration; 2) determine effects an oral wound‐healing model; 3) identify...
Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for treatment of hypertension either alone or in combination with other antihypertensives. HCTZ mainly cleared by kidney via tubular secretion, but underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters [human transporter 1 (hOAT1), human 3 (hOAT3), 2 (hOCT2), multidrug toxin extrusion (hMATE1), 2-K (hMATE2-K)], we found that interacted both transporters....
Research Articles| March 23 2010 Der Nachweis von Trophoblastzellen im strömenden Blut der Frau bei normaler und gestörter Gravidität Subject Area: Further Areas , Women's and Children's Health D. Wagner; Wagner Aus Universitäts-Frauenklinik Freiburg/Br. (Direktor: Prof. Dr. H. Wimhöfer) Search for other works by this author on: This Site PubMed Google Scholar R. Schunck; Schunck Isebarth Gynaecologia (1964) 158 (3): 175–192. https://doi.org/10.1159/000303776 Article history Published...
1. Beta-carbolines are indole alkaloids with a wide range of pharmacological and toxicological activities. structurally related to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), known substrate organic cation transporters (OCTs). The goal this study is determine interaction β-carbolines human OCT1, 2, 3 (SLC22A1-3). 2. Dose-dependent inhibition studies were performed for five commercially available using fluorescent assay in HEK293 cells stably expressing hOCT1-3. potential was evaluated...
The objective of this work is to develop extended release subcutaneous thermo-responsive in situ gel-forming delivery systems using the following commercially available triblock polymers: poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly acid) (PLGA-PEG-PLGA, copolymer A & B) and (lactide-co-caprolactone)-poly (lactide-co-caprolactone) (PLCL-PEG-PLCL, C). Performance two optimized formulations containing ketoprofen as a model compound, was assessed by comparing vitro drug profiles...