Publications by authors named "Philipp Buchgraber"

This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay.

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Article Synopsis
  • The study focuses on the discovery and optimization of new soluble guanylate cyclase (sGC) stimulators, which have potential therapeutic benefits for various conditions.
  • Researchers utilized ultrahigh-throughput screening to identify a new class of sGC stimulators, improving key properties like potency and solubility during the optimization process.
  • The result is BAY 1165747 (BAY-747), a promising treatment for resistant hypertension, showing effective hemodynamic results lasting up to 24 hours in early clinical trials.
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Eukaryotes have evolved two major pathways to repair potentially lethal DNA double-strand breaks. Homologous recombination represents a precise, DNA-template-based mechanism available during the S and G2 cell cycle phase, whereas non-homologous end joining, which requires DNA-dependent protein kinase (DNA-PK), allows for fast, cell cycle-independent but less accurate DNA repair. Here, we report the discovery of , a novel selective inhibitor of DNA-PK.

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The excited-state dynamics of a series of Wurster's salts (p-phenylenediamine radical cations) with different subtituents on the nitrogen atoms was investigated under a variety of experimental conditions using a combination of ultrafast spectroscopic techniques. At room temperature, the lifetime of the lowest excited state of all radical cations is on the order of 200 fs, independently of the solvent, that is, water, nitriles, alcohols, and room-temperature ionic liquid. On the other hand, all cations, except that with the bulky nitrogen substituents, become fluorescent below 120 K.

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A productive total synthesis of both enantiomers of berkelic acid (1) is outlined that takes the structure revision of this bioactive fungal metabolite previously proposed by our group into account. The successful route relies on a fully optimized triple-deprotection/1,4-addition/spiroacetalization cascade reaction sequence, which delivers the tetracyclic core 32 of the target as a single isomer in excellent yield. The required cyclization precursor 31 is assembled from the polysubstituted benzaldehyde derivative 20 and methyl ketone 25 by an aldol condensation, in which the acetyl residue in 20 transforms from a passive protecting group into an active participant.

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