A5069927005- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Microbial Natural Products and Biosynthesis
- Hedgehog Signaling Pathway Studies
- Cell Image Analysis Techniques
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Wnt/β-catenin signaling in development and cancer
- Protein Degradation and Inhibitors
- Tryptophan and brain disorders
- Asymmetric Synthesis and Catalysis
- Alkaloids: synthesis and pharmacology
- Cancer-related gene regulation
- Chemical synthesis and alkaloids
- Medical Imaging Techniques and Applications
- Phytochemical compounds biological activities
- Alzheimer's disease research and treatments
- Glycosylation and Glycoproteins Research
- Catalytic C–H Functionalization Methods
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
Max Planck Institute of Molecular Physiology
2016-2025
Klinik und Poliklinik für Nuklearmedizin
2017-2025
LMU Klinikum
2021-2025
Ludwig-Maximilians-Universität München
2019-2025
Medizinische Hochschule Hannover
2025
Max Planck Society
2007-2023
Robert Bosch (Germany)
2023
München Klinik
2017-2022
Benaroya Research Institute
2020
TU Dortmund University
2013-2018
The limited structural diversity that a compound library represents severely restrains the discovery of bioactive small molecules for medicinal chemistry and chemical biology research, thus calls developing new divergent synthetic approaches to structurally diverse complex scaffolds. Here we present de novo branching cascades approach wherein simple primary substrates follow different cascade reactions create various distinct molecular frameworks in scaffold phase. Later, elaboration phase...
Current therapies for common types of cancer such as renal cell are often ineffective and unspecific, novel pharmacological targets approaches in high demand. Here we show the unexpected possibility rapid selective killing cells through activation calcium-permeable nonselective transient receptor potential canonical (TRPC) calcium channels by sesquiterpene (-)-englerin A. This compound was found to be a highly efficient, fast-acting, potent, selective, direct stimulator TRPC4 TRPC5 channels....
Abstract Herein, we report the first enantioselective annulation of α‐arylidene pyrazolones through a formal C(sp 3 )−H activation under mild conditions enabled by highly variable Rh III ‐Cp x catalysts. The method has wide substrate scope and proceeds with good to excellent yields enantioselectivities. Its synthetic utility was demonstrated late‐stage functionalization drugs natural products as well preparation enantioenriched [3]dendralenes. Preliminary biological investigations also...
Abstract Axially chiral 4‐arylisoquinolones are endowed with pronounced bioactivity, and methods for their efficient synthesis have gained widespread attention. However, enantioselective of axially by means C−H activation has not been reported to date. Described here is a rhodium (III)‐catalyzed bond annulation the atroposelective 4‐arylisoquinolones. The method employs cyclopentadienyl ligands embodying piperidine ring as backbone yields atropisomers good excellent enantioselectivity....
Abstract Bioactive compound design based on natural product (NP) structure may be limited because of partial coverage NP‐like chemical space and biological target space. These limitations can overcome by combining NP‐centered strategies with fragment‐based through combination NP‐derived fragments to afford structurally unprecedented “pseudo‐natural products” (pseudo‐NPs). The design, synthesis, evaluation a collection indomorphan pseudo‐NPs that combine biosynthetically unrelated indole‐...
Abstract The imino Diels–Alder reaction is an efficient method for the synthesis of aza‐heterocycles. While different stereo‐ and enantioselective inverse‐electron‐demand (IEDIDA) reactions have been reported before, IEDIDA including electron‐deficient dienes are unprecedented. first between electron‐poor chromone cyclic imines, catalyzed by zinc/binol complexes described. novel provides a facile entry to natural product inspired collection ring‐fused quinolizines potent modulator mitosis.
The large-scale synthesis of englerin A (see scheme) and subsequent structure-activity relationship studies have led to the discovery highly potent analogues. TBS=tert-butyldimethylsilyl. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: publisher is responsible for content functionality any supporting information supplied Any queries...
Aberrant hedgehog (Hh) signaling contributes to the pathogenesis of multiple cancers. Available inhibitors target Smoothened (Smo), which can acquire mutations causing drug resistance. Thus, compounds that inhibit Hh downstream Smo are urgently needed. We identified dynarrestin, a novel inhibitor cytoplasmic dyneins 1 and 2. Dynarrestin acts reversibly dynein 1-dependent microtubule binding motility in vitro without affecting ATP hydrolysis. It rapidly inhibits endosome movement living cells...
Unbiased morphological profiling of bioactivity, for example, in the cell painting assay (CPA), enables identification a small molecule's mode action based on its similarity to bioactivity reference compounds, irrespective biological target or chemical similarity. This is particularly important molecules with nonprotein targets as these are rather difficult identify widely employed target-identification methods. We using CPA compounds that biosimilar iron chelator deferoxamine. Structurally...
Abstract The efficient exploration of biologically relevant chemical space is essential for the discovery bioactive compounds. A molecular design principle that possesses both biological relevance and structural diversity may more efficiently lead to compound collections are enriched in diverse bioactivities. Here pseudo-natural product (PNP) strategy, which combines PNP concept with synthetic diversification strategies from diversity-oriented synthesis, reported. collection was synthesized...
Rac proteins of the Rho-like GTPase family, including ubiquitous Rac1, hematopoiesis-specific Rac2, and least-characterized Rac3 play a major role in oncogenic transformation, tumor invasion metastasis. However, prognostic relevance expression human tumors has not been investigated yet. In present study, protein was analyzed benign secretory epithelium, high-grade prostatic intraepithelium neoplasia (HG-PIN), prostate carcinomas 60 R0-resected radical prostatectomy specimens by...
A Prins cyclization between a polymer-bound aldehyde and homoallylic alcohol served as the key step in synthesis of tetrahydropyran derivatives. phenotypic screen led to identification compounds that inhibit mitosis (as seen by accumulation round cells with condensed DNA membrane blebs; see picture). These were termed tubulexins they target CSE1L protein vinca alkaloid binding site tubulin.
Cousins you can count on: An iridoid-inspired compound collection was synthesized efficiently by the resolution of cyclic enones in an asymmetric cycloaddition with azomethine ylides. The contained novel potent inhibitors Wnt and Hedgehog signaling pathways.
Abstract The selective transformation of different starting materials by metal catalysts under individually optimized reaction conditions to structurally intermediates and products is a powerful approach generate diverse molecular scaffolds. In more unified albeit synthetically challenging strategy, common would be exposed catalysis, leading intermediate giving rise scaffolds tuning the reactivity catalyst through ligands. Herein we present ligand-directed synthesis for gold(I)-catalysed...
Abstract Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide of compound collections enriched bioactivity. The trans ‐hydrindane dehydro‐δ‐lactone motif defines characteristic scaffold steroid‐like withanolides, a plant‐derived product class with diverse pattern A withanolide‐inspired collection was synthesized by making use three key intermediates that contain this framework derivatized different reactive functional groups. Biological...