A5053563894- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Cholesterol and Lipid Metabolism
- Eicosanoids and Hypertension Pharmacology
- Computational Drug Discovery Methods
- Synthesis and biological activity
- X-ray Diffraction in Crystallography
- Prostate Cancer Treatment and Research
- Crystallization and Solubility Studies
- Synthesis of heterocyclic compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer therapeutics and mechanisms
- Synthesis and Reactions of Organic Compounds
- Mass Spectrometry Techniques and Applications
- Sulfur-Based Synthesis Techniques
- Receptor Mechanisms and Signaling
- Advanced Breast Cancer Therapies
- Heat shock proteins research
- Genetics, Bioinformatics, and Biomedical Research
- PARP inhibition in cancer therapy
- Hormonal Regulation and Hypertension
- Science, Research, and Medicine
- Molecular Biology Techniques and Applications
- Radiation Therapy and Dosimetry
- Breast Cancer Treatment Studies
Karlsruhe Institute of Technology
2014-2025
Abstract Results of scientific work in chemistry can usually be obtained the form materials and data. A big step towards transparency reproducibility gained if scientists publish their data research repositories a FAIR manner. Nevertheless, order to make sustainable discipline, obtaining is insufficient comprehensive concept that includes preservation needed. In offer infrastructure find access were generated projects, we combined Chemotion repository with an archive for chemical compounds....
A solid supported procedure for the synthesis of benzoxazinones, dihydropyrazinones, quinoxalinones, and dihydrooxazinones using immobilized oxazolones in combination with difunctional nucleophiles as cleavage agent is presented. The scope novel method has been demonstrated through subsequent modification parent oxazolone scaffold on supports conversions electrophiles or CuAAC reactions to give functionalized pyrazin-2-ones. described allows target heterocycles good yields via three five...
In macrophages, transient receptor potential vanilloid 2 (TRPV2) channel contributes to various cellular processes such as cytokine production, differentiation, phagocytosis and migration. Due a lack of selective pharmacological tools, its function in immunological is not well understood the identification novel TRPV2 modulators highly desirable.Novel were identified by screening compound library using Ca2+ influx assays with human embryonic kidney 293 (HEK293) cells heterologously...
A solid supported, odorless reagent for the dithioacetalization of aldehydes and ketones has been developed. The new provides dimercaptoalkane equivalent in combination with stoichiometric amounts immobilized acid enables formation dithianes dithiolanes from without any additives good to very yields high purities. reaction is chemoselective aldehydes, but can be reacted corresponding dithioketals if an additional Lewis such as BF3 added.
Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson's disease, Alzheimer's disease. Clinical studies demonstrate a reduction mentioned diseases' symptoms after administration anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced...
BAG1 is a family of polypeptides with conserved C-terminal BAG domain that functions as nucleotide exchange factor for the molecular chaperone HSP70. proteins also control several signaling processes including proteostasis, apoptosis, and transcription. The largest isoform, BAG1L, controls activity androgen receptor (AR) upregulated in prostate cancer. Here, we show BAG1L regulates AR dynamics nucleus its ablation attenuates target gene expression especially those involved oxidative stress...
The pro-oncogenic activities of estrogen receptor alpha (ERα) drive breast cancer pathogenesis. Endocrine therapies that impair the production or action ERα are therefore used to prevent primary disease metastasis. Although recent successes with degraders have been reported, there is still need develop further antagonists additional properties for therapy. We previously described a benzothiazole compound A4B17 inhibits proliferation androgen receptor–positive prostate cells by disrupting...
All current clinically approved androgen deprivation therapies for prostate cancer target the C-terminal ligand-binding domain of receptor (AR). However, main transactivation function is localized at AR N-terminal (NTD). Targeting NTD directly a challenge because its intrinsically disordered structure and lack pockets drugs to bind. Here, we have taken an alternative approach using cochaperone BAG1L, which interacts with NTD, develop novel inhibitor. We describe identification...
Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR drives transcriptional activity CRPC remains a challenging therapeutic target. Herein we demonstrate BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with pathways, including signaling, are implicated development progression CRPC. In addition, interrogation geometric physiochemical...
Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these The G-protein coupled receptor 55 (GPR55) broadly expressed in central nervous tissues cells involved the regulation inflammatory cell homeostasis. We have recently shown that coumarin-based compounds enfold inverse agonistic activities at GPR55 resulting inhibition prostaglandin E2....
The conversion of dithianylium cations into α-azo ketene dithioacetals via addition polymer-bound diazonium precursors is shown. This new procedure allows the synthesis in one step within 2–90 min at rt and yields highly pure compounds that do not have to be purified most cases. obtained been shown valuable intermediates for hydrazones, α-halogenated dithioacetals, azo-functionalized dienes.
Abstract Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Nematocyst discharge is controlled a mechanosensory apparatus with analogies to vertebrate hair cells. Members transient receptor potential (TRPN) ion channel family supposed be involved in transduction mechanical stimulus. A small molecule screen was performed identify compounds that affect nematocyst Hydra . We identified several...
Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and chemokines, c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C (CXCL2), CXCL10. Inflammatory processes of the central nervous system (CNS) play an important role in pathogenesis various neurological psychiatric disorders like Alzheimer’s disease, Parkinson’s depression. Therefore, identifying novel anti-inflammatory drugs may be beneficial for treating with a...
A synthesis route to access triazole–pyrazole hybrids via triazenylpyrazoles was developed. Contrary existing methods, this allows the facile N -functionalization of pyrazole before attachment triazole unit a copper-catalyzed azide–alkyne cycloaddition. The developed methodology used synthesize library over fifty new multi-substituted pyrazole–triazole hybrids. We also demonstrate one-pot strategy that renders isolation potentially hazardous azides obsolete. In addition, compatibility method...
<p>BAG-1 knockout female mice are fertile and viable with reduced gestation.</p>
<p>Thio-2 reduces genome-wide androgen receptor binding in LNCaP prostate cancer cells.</p>
<p>Thio-2 downregulates C-MYC expression through a BAG-1 independent mechanism.</p>
<p>In-vivo treatment of patient derived model lethal prostate cancer demonstrates Thio-2 to be well tolerated with associated impact on AR signaling and growth.</p>
<p>Thio-2, may bind the N-terminus of androgen receptor through a similar binding mode to EPI-001.</p>
<p>Thio-2 solubility.</p>
<p>Treatment with Thio-2 inhibits transactivation of the unstimulated and stimulated androgen receptor constitutively active splice variant-7.</p>
<p>Mouse organ hematoxylin and eosin, BAG-1 immunohistochemistry, in knockout mice.</p>
<p>BAG-1 knockout female mice are fertile and viable with reduced gestation.</p>