A5057555641- Estrogen and related hormone effects
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- Computational Drug Discovery Methods
- Colorectal Cancer Treatments and Studies
- Receptor Mechanisms and Signaling
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Cytokine Signaling Pathways and Interactions
- Neurotransmitter Receptor Influence on Behavior
- Endometriosis Research and Treatment
- Reproductive System and Pregnancy
- Neuropeptides and Animal Physiology
- Steroid Chemistry and Biochemistry
- Pharmacogenetics and Drug Metabolism
- Chemical Reactions and Isotopes
- Protein Structure and Dynamics
- Radiopharmaceutical Chemistry and Applications
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Chemokine receptors and signaling
- Nicotinic Acetylcholine Receptors Study
MSD (Netherlands)
2010-2011
Amsterdam University of Applied Sciences
2011
Merck (Netherlands)
2011
Netherlands eScience Center
2011
Radboud University Medical Center
2010
Universidade Federal de São Paulo
2010
Radboud University Nijmegen
2010
The Netherlands Cancer Institute
1988-1989
Oncode Institute
1988
Highly purified peripheral blood monocytes were cultured in the presence of rIL-4. Major changes morphology observed. After day 5 culturing cells acquired a macrophage-like appearance, with increased cell size and extensive processes, suggesting that IL-4 may induce monocyte-macrophage differentiation. This notion is supported by observed expression MHC class II Ag, which thought to be associated monocyte Exposure resulted dose-dependent increase became apparent after only 20 h incubation....
Abstract Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators simultaneously modulate tumor immunity and another oncogenic pathway then used it identify 38 candidate immune–metabolic regulators. We show activities of these stratify patients with melanoma by their response anti–PD-1 using machine learning deep neural approaches, which...
The GPCRDB is a Molecular Class-Specific Information System (MCSIS) that collects, combines, validates and disseminates large amounts of heterogeneous data on G protein-coupled receptors (GPCRs). contains experimental sequences, ligand-binding constants, mutations oligomers, as well many different types computationally derived such multiple sequence alignments homology models. provides access to the via number methods. It offers visualization analysis tools, query systems. updated...
The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because its successful application medicinal chemistry and, particular, high-throughput virtual screening (HTVS). simplicity the definition enables complexity molecular interactions between ligand and receptor to be reduced a handful set features. With many softwares available, it utmost interest explore behavior these tools when applied different biological systems. In this work, we present...
Protein structure-based pharmacophore (SBP) models derive the molecular features a ligand must contain to be biologically active by conversion of protein properties reciprocal space. SBPs improve understanding ligand–protein interactions and can used as valuable tools for hit lead optimization, compound library design, target hopping.
Neoadjuvant chemoradiotherapy (nCRT) improves outcomes in resectable esophageal adenocarcinoma (EAC), but acquired resistance precludes long-term efficacy. Here, we delineate these mechanisms. RNA sequencing on matched patient samples obtained pre-and post-neoadjuvant treatment reveal that oxidative phosphorylation was the most upregulated of all biological programs following nCRT. Analysis patient-derived models confirms mitochondrial content and oxygen consumption strongly increase...
G-protein coupled receptors (GPCRs) are important drug targets for various diseases and of major interest to pharmaceutical companies. The function individual members this protein family can be modulated by the binding small molecules at extracellular side structurally conserved transmembrane (TM) domain. Here, we present Snooker, a structure-based approach generate pharmacophore hypotheses compounds TM Snooker does not require knowledge ligands, is therefore suitable apo-proteins, applied...
Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone (P) or oestradiol and (17beta-E(2)+P) menstrual treated 17beta-E(2)+P. Gene expression validated real-time PCR in the samples used for arrays, collected from early mid-secretory endometrium, additional experiments new phase. The results show that is more responsive to progestins than several genes associated embryo implantation (i.e. thrombomodulin, monoamine...
Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is potent (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability rat (F(po) 4%) possessed off-target activity at hERG ion channel (pK(i) 5.5). Systematic modification physicochemical properties, such lipophilicity basicity, used...
We present the systematic prospective evaluation of a protein-based and ligand-based virtual screening platform against set three G-protein-coupled receptors (GPCRs): β-2 adrenoreceptor (ADRB2), adenosine A(2A) receptor (AA2AR), sphingosine 1-phosphate (S1PR1). Novel bioactive compounds were identified using consensus scoring procedure combining (frequent substructure ranking) structure-based (Snooker) tools, all 900 selected screened receptors. A striking number ligands showed...
Abstract Background G-protein coupled receptors (GPCRs) are involved in many different physiological processes and their function can be modulated by small molecules which bind the transmembrane (TM) domain. Because of structural sequence conservation, TM domains often used bioinformatics approaches to first create a multiple alignment (MSA) subsequently identify ligand binding positions. So far methods have been developed predict common residue positions for class A GPCRs. Results Here we...
Here we report the cloning of a gene encoding new member superfamily G protein‐coupled receptors. The encodes protein 365 amino acids closely resembling two recently cloned nucleotide binding receptors, called P 2U and 2Y purinoceptors (71% 49% sequence identity within transmembrane domains, respectively). Our studies show that this putative purinoceptor (designated 2P ) is encoded by an intronless single copy exclusively expressed in pancreas, contrast to which are widely distributed...
Recently the first community-wide assessments of prediction structures complexes between proteins and small molecule ligands have been reported in so-called GPCR Dock 2008 2010 assessments. In current review we discuss different steps along protein-ligand modeling workflow by critically analyzing strategies used to predict submitted recent challenge. These representative test cases, focusing on pharmaceutically relevant G Protein-Coupled Receptors, are demonstrate strengths challenges...
Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) cytoreductive surgery in resectable patients shows limited benefit, novel treatments urgently needed. The majority CRC-PMs represent CMS4 molecular subtype CRC, here we queried vulnerabilities this pharmacogenomic databases identify therapies. This reveals copper ionophore elesclomol...
The quality of three-dimensional homology models derived from protein sequences provides an independent measure the suitability a sequence for certain fold. We have used automated modeling and model assessment tools to identify putative nuclear hormone receptor ligand-binding domains in genome Caenorhabditis elegans. Our results indicate that availability multiple crystal structures is crucial obtaining useful this family. majority annotated mammalian receptors could be assigned domain fold...
<div>Abstract<p>Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an <i>in silico</i> multiomics approach (BipotentR) to find cancer cell–specific regulators simultaneously modulate tumor immunity and another oncogenic pathway then used it identify 38 candidate immune–metabolic regulators. We show activities of these stratify patients with melanoma by their response anti–PD-1 using machine...
<div>Abstract<p>Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an <i>in silico</i> multiomics approach (BipotentR) to find cancer cell–specific regulators simultaneously modulate tumor immunity and another oncogenic pathway then used it identify 38 candidate immune–metabolic regulators. We show activities of these stratify patients with melanoma by their response anti–PD-1 using machine...