A5071463749- Cancer, Stress, Anesthesia, and Immune Response
- Immune cells in cancer
- Fungal and yeast genetics research
- Enzyme Structure and Function
- Tryptophan and brain disorders
- Genomics and Chromatin Dynamics
- Nanoplatforms for cancer theranostics
- DNA Repair Mechanisms
- Crystal structures of chemical compounds
- Adenosine and Purinergic Signaling
- Synthesis and biological activity
- ATP Synthase and ATPases Research
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Ion Transport and Channel Regulation
- Polyamine Metabolism and Applications
- Renal and related cancers
- Biochemical and Molecular Research
- Cancer-related Molecular Pathways
- Microbial Metabolic Engineering and Bioproduction
- interferon and immune responses
Bayer (Germany)
2008-2023
Nuvisan (Germany)
2023
Max Planck Institute for Molecular Genetics
2005
Max Planck Society
2002
Background The metabolism of tryptophan to kynurenines (KYN) by indoleamine-2,3-dioxygenase or tryptophan-2,3-dioxygenase is a key pathway constitutive and adaptive tumor immune resistance. immunosuppressive effects KYN in the microenvironment are predominantly mediated aryl hydrocarbon receptor (AhR), cytosolic transcription factor that broadly suppresses cell function. Inhibition AhR thus offers an antitumor therapy opportunity via restoration system functions. Methods expression was...
MTH1 is a hydrolase responsible for sanitization of oxidized purine nucleoside triphosphates to prevent their incorporation into replicating DNA. Early tool compounds published in the literature inhibited enzymatic activity and subsequently induced cancer cell death; however recent studies have questioned reported link between these two events. Therefore, it important validate as dependency with high quality chemical probes. Here, we present BAY-707, substrate-competitive, highly potent...
Aldosterone is the principal hormonal regulator of sodium homeostasis in vertebrates. It exerts its actions through mineralocorticoid receptor (MR) that regulates transcription specific target genes. In recent years, a number MR genes have been identified are involved regulation epithelial channel (ENaC), key modulator renal absorption. Here we report identification cnksr3 as direct gene up-regulated response to physiological concentrations aldosterone. The promoter exhibits two functional...
The serine/threonine kinase TBK1 (TANK-binding 1) and its homologue IKKε are noncanonical members of the inhibitor nuclear factor κB (IκB) family. These kinases play important roles in multiple cellular pathways and, particular, inflammation. Herein, we describe our investigations on a family benzimidazoles identification potent highly selective TBK1/IKKε BAY-985. BAY-985 inhibits phosphorylation interferon regulatory 3 displays antiproliferative efficacy melanoma cell line SK-MEL-2 but...
Heterochromatinization at the silent mating-type loci HMR and HML in Saccharomyces cerevisiae is achieved by targeting Sir complex to these regions via a set of anchor proteins that bind silencers. Here, we have identified novel heterochromatin-targeting factor for , protein Sum1, repressor meiotic genes during vegetative growth. Sum1 bound both vitro vivo functional element within -E silencer, sum1 Δ caused derepression. Significantly, was also required origin activity -E, demonstrating...
Replication initiation at origins of replication in the yeast genome takes place on chromatin as a template, raising question how histone modifications, for instance acetylation, influence origin firing. Initiation requires binding initiator, Origin Recognition Complex (ORC), to consensus sequence within origins. In addition, other proteins bind recognition sites vicinity ORC and support initiation. previous work, we identified Sum1 an origin-binding protein that contributes efficient is...
PIP4K2A is an insufficiently studied type II lipid kinase that catalyzes the conversion of phosphatidylinositol-5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI4,5P2). The involvement PIP4K2A/B in cancer has been suggested, particularly context p53 mutant/null tumors. depletion shown to induce tumor growth inhibition, possibly due hyperactivation AKT and reactive oxygen species-mediated apoptosis. Herein, we report identification novel potent highly selective inhibitors...
Abstract Re-constitution of anti-tumor T-cell responses by clinically-approved immune checkpoint inhibitors (ICIs) targeting CTLA4 or PD-1/PD-L1 represents a breakthrough cancer therapy. Nevertheless, substantial number patients do not benefit from these new therapeutic modalities chiefly due to local immunosuppression in the tumor microenvironment. In addition, long circulation time ICIs restricts options modify dosing regimens for management adverse effects. Oral small molecule as next...
Abstract Tumor cells co-opt multiple pathways in order to evade attack by infiltrating immune cells. One such mechanism is the upregulation of indole-2,3-dioxygenase (IDO1) and/or tryptophan-2,3-dioxygenase (TDO2), both which are first-step, rate-limiting enzymes degrading tryptophan immunosuppressive metabolites kynurenine (KYN) and kynurenic acid (KA). KYN KA bind activate aryl hydrocarbon receptor (AhR), expressed many cell types well known for its effects. Targeting AhR with an inhibitor...
Abstract Cancer cells are characterized by an increase in the rate of reactive oxygen species (ROS) production and altered redox environment compared to normal cells. The role ROS tumorigenesis is two-fold. On one hand, play a causal tumor development progression inducing genomic instability aberrant, pro-tumorigenic signalling. other high levels can also be toxic cancer cells, oxidizing damaging both DNA free nucleotides (dNTPs), which lead cell death. MutT Homolog 1 (MTH1) redox-protective...
The human pituitary adenylate cyclase-activating polypeptide receptor (hPAC1-R), a class B G-protein-coupled (GPCR) identified almost 30 years ago, represents an important pharmacological target in the areas of neuroscience, oncology, and immunology. Despite interest this target, only very limited number small molecule modulators have been reported for receptor. We herein describe results drug discovery program aiming identification potent selective hPAC1-R antagonist. An initial...
Abstract Cancer cells can form reactive oxygen species (ROS) due to altered redox regulation that affect desoxynucleosides triphosphates (dNTP) in particular. 8-oxo-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP) and 2-hydroxydeoxyadenosine-5'-triphosphate (2-OH-dATP) are the two most abundant oxidative nucleotide lesions this respect. These undesired nucleoside sanitized by hydrolase MTH1 (also known as NUDT1) order prevent their incorporation into replicating DNA. Sprint Bioscience created...
Tumor cells co-opt multiple pathways in order to evade attack by infiltrating immune cells. One such mechanism is the upregulation of indole-2,3-dioxygenase (IDO1) and/or tryptophan-2,3-dioxygenase (TDO2), both which are first-step, rate-limiting enzymes degrading tryptophan immunosuppressive metabolites kynurenine (KYN) and kynurenic acid (KA). KYN KA bind activate aryl hydrocarbon receptor (AhR), expressed many cell types well known for its effects. Targeting AhR with an inhibitor may...
Re-constitution of anti-tumor T-cell responses by clinically-approved immune checkpoint inhibitors (ICIs) targeting CTLA4 or PD-1/PD-L1 represents a breakthrough cancer therapy. Nevertheless, substantial number patients do not benefit from these new therapeutic modalities chiefly due to local immunosuppression in the tumor microenvironment. In addition, long circulation time ICIs restricts options modify dosing regimens for management adverse effects. Oral small molecule as next generation...