A5022172576- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Nuclear Physics and Applications
- Glycosylation and Glycoproteins Research
- Nitric Oxide and Endothelin Effects
- Nuclear physics research studies
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- Lanthanide and Transition Metal Complexes
- Chemical Synthesis and Analysis
- Cancer, Hypoxia, and Metabolism
- Nuclear reactor physics and engineering
- Hemoglobin structure and function
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Microbial Natural Products and Biosynthesis
- Chronic Lymphocytic Leukemia Research
- Enzyme function and inhibition
- Vitamin K Research Studies
- Dermatology and Skin Diseases
- Pharmacological Receptor Mechanisms and Effects
- Marine Sponges and Natural Products
- Advanced Measurement and Metrology Techniques
- Quinazolinone synthesis and applications
Bayer (Germany)
2007-2024
Nuvisan (Germany)
2021-2024
University of Patras
2014
Freie Universität Berlin
2009
Institut de Neurobiologie de la Méditerranée
2007
Inserm
2007
University of Milan
2005
University of Göttingen
1991-2002
Humboldt-Universität zu Berlin
1999
New isomeric states in the neutron-rich nuclei near $Z\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}28$ and $N\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}40$ shell closures have been identified among reaction products of a $60.3A$ MeV ${}^{86}\mathrm{Kr}$ beam on ${}^{\mathrm{nat}}\mathrm{Ni}$ target. From measured decay properties information about excited their nuclear structure has obtained. The isomerism is related mostly to occupation neutron ${g}_{9/2}$ orbital, an intruder...
Abstract The phosphoinositide 3‐kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or the genetic mutation and amplification of key components. A variety PI3K isoforms play differential roles cancers. As such, development inhibitors from novel compound classes should lead to pharmacological pharmacokinetic profiles allow exploration various indications, combinations, dosing regimens. screening effort...
Heme is a vital molecule for all life forms with heme being capable of assisting in catalysis, binding ligands, and undergoing redox changes. Heme-related dysfunction can lead to cardiovascular diseases the oxidation soluble guanylyl cyclase (sGC) critically implicated some these diseases. sGC, main nitric oxide (NO) receptor, stimulates second messenger cGMP production, whereas reactive oxygen species are known scavenge NO oxidize/inactivate leading sGC degradation. This vulnerability...
Herein we describe the discovery, mode of action, and preclinical characterization soluble guanylate cyclase (sGC) activator runcaciguat. The sGC enzyme, via formation cyclic guanosine monophoshphate, is a key regulator body tissue homeostasis. activators with their unique action are activating oxidized heme-free therefore NO-unresponsive form sGC, which formed under oxidative stress. first generation like cinaciguat or ataciguat exhibited limitations were discontinued. We overcame...
The soluble guanylyl cyclase (sGC) is an important receptor for nitric oxide (NO). Nitric activates sGC several hundred fold to generate cGMP from GTP. Because of sGC's salutary roles in cardiovascular physiology, it has received substantial attention as a drug target. heme domain key its regulation not only contains the NO activation site but also harbors sites NO-independent activators well S-nitrosylation (β1 C122) involved desensitization. Here we report crystal structure activator BAY...
Factor XI (FXI), the zymogen of activated FXI (FXIa), is an attractive target for novel anticoagulants because inhibition offers potential to reduce thrombosis risk while minimizing bleeding. BAY 1213790, a anti-FXIa antibody, was generated using phage display technology. Crystal structure analysis FXIa-BAY 1213790 complex demonstrated that tyrosine-rich complementarity-determining region 3 loop heavy chain penetrated deepest into FXIa binding epitope, forming network favorable interactions...
Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic target as it contributes to the development and progression of thrombosis but thought play only minor role in hemostasis so that its inhibition may allow for decoupling efficacy bleeding time prolongation. Herein, we report our major efforts identify an orally bioavailable, reversible FXIa inhibitor. Using protein structure-based de novo design approach, identified novel micromolar hit with physicochemical...
Herein, we describe the identification, chemical optimization, and preclinical characterization of novel soluble guanylate cyclase (sGC) stimulators. Given very broad therapeutic opportunities for sGC stimulators, new tailored molecules distinct indications with specific pharmacokinetics, tissue distribution, physicochemical properties will be required in future. Here, report ultrahigh-throughput (uHTS)-based discovery a class stimulators from an imidazo[1,2-a]pyridine lead series. Through...
The concentration of clobetasol propionate in the stratum corneum after application three different formulations was determined, quantifying influence on bioavailability drug. sampled by tape stripping. concentrations were determined quantitatively HPLC. After Clobetasol Propionate Cream USP, 0.05%, and Temovate Cream, identical amounts drug found corneum, whereas ε Emollient, quantity clearly decreased. From results obtained measuring adjacent sites skin where creams had not been applied,...
Despite extensive research on small molecule thrombin inhibitors for oral application in the past decades, only a single double prodrug with very modest bioavailability has reached human therapy as marketed drug. We have undertaken major efforts to identify neutral, non-prodrug inhibitors. Using holistic analysis of all available internal data, we were able build computational models and apply these selection lead series highest possibility achieving bioavailability. In our design, relied...
The matrix metalloprotease ADAMTS7 has been identified by multiple genome-wide association studies as being involved in the development of coronary artery disease. Subsequent research revealed proteolytic function enzyme to be relevant for atherogenesis and restenosis after vessel injury. Based on a publicly known dual ADAMTS4/ADAMTS5 inhibitor, we have silico designed an inhibitor catalytic domain, which served starting point optimization campaign. Initially our inhibitors suffered from low...
1. In the laboratory, a microcosm experiment was set up to study (1) interaction between two collembolan species Onychiurus furcifer (Börner) and Heteromurus nitidus (Templeton) during 24 weeks of incubation; (2) influence slug ( Arion rufus L.) cast material on outcome this interaction; (3) activity microbial biomass, respiration nutrient mobilization. 2. The CO 2 production monitored every other week NH 4 + , NO 3 – PO 3– contents leachates were determined weeks. After 12 incubation,...
Abstract DHODH is a key enzyme in the biosynthesis of pyrimidines and recent studies have renewed interest this old anti-cancer target. Here, we disclose discovery 4-triazolosalicylamides as inhibitors their structure activity relationship (SAR). The hit cluster was discovered during phenotypic high throughput screen (HTS) 2.5 million compounds where proliferation H460 lung cancer cells used read-out. successfully identified molecular target by comparing profile hits panel cell lines to set...
The -decay study of the neutron drip line nuclei , and is presented. These were produced by fragmentation 95 MeV/ projectiles on a target. separated doubly achromatic projectile-fragment separator RIPS, implanted into stopper to observe their decays. half-lives -delayed emission probabilities preliminarily determined for first time.
A key prerequisite for the successful application of protein crystallography in drug discovery is to establish a robust crystallization system new drug-target fast enough deliver crystal structures when first inhibitors have been identified hit-finding campaign or, at latest, subsequent hit-to-lead process. The crucial step towards generating well folded proteins with high likelihood crystallizing identification suitable truncation variants target protein. In some cases an optimal length...
DHODH is a key enzyme in the biosynthesis of pyrimidines and recent studies have renewed interest this old anti-cancer target. Here, we disclose discovery 4-triazolosalicylamides as inhibitors their structure activity relationship (SAR). The hit cluster was discovered during phenotypic high throughput screen (HTS) 2.5 million compounds where proliferation H460 lung cancer cells used read-out. successfully identified molecular target by comparing profile hits panel cell lines to set with...
Abstract For see ChemInform in Full Text.
Abstract Immune checkpoint blockade using antibodies targeting the cell surface expressed proteins CTLA-4, PD-1 and PD-L1 has revolutionized cancer care its clinical impact in several indications prompted a search for complementary immunostimulatory approaches that can further increase efficacy of these drugs. Mitogen-activated protein kinase 1 (MAP4K1; HPK1), serine/threonine exclusively hematopoietic lineages, mediates negative feedback signal downstream T-cell receptor stimulation. Its...