A5007352773- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Synthetic Organic Chemistry Methods
- Ubiquitin and proteasome pathways
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Catalytic C–H Functionalization Methods
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Software Testing and Debugging Techniques
- Histone Deacetylase Inhibitors Research
- Cell death mechanisms and regulation
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Microbial Natural Products and Biosynthesis
- Synthesis and Catalytic Reactions
- Neuropeptides and Animal Physiology
- RNA Interference and Gene Delivery
Dana-Farber Cancer Institute
2015-2021
University of Copenhagen
2020
Danish Geotechnical Society
2017
Technical University of Denmark
2011-2017
Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class ligands that promote meta-C-H arylation anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables wide substrate coupling partner scope. Meta-C-H with aryl iodides partners is also realized for first time ligand. The utility transformation drug discovery showcased by...
Protein degradation is an emerging therapeutic strategy with a unique molecular pharmacology that enables the disruption of all functions associated target. This particularly relevant for proteins depending on scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs). To address tractability multiple RTKs chemical by E3 ligase CUL4-RBX1-DDB1-CRBN (CRL4CRBN), we synthesized series phthalimide degraders based promiscuous kinase inhibitors sunitinib and PHA665752. While...
Most intracellular proteins lack hydrophobic pockets suitable for altering their function with drug-like small molecules. Recent studies indicate that some undruggable can be targeted by compounds degrade them. For example, thalidomide-like drugs (IMiDs) the critical multiple myeloma transcription factors IKZF1 and IKZF3 recruiting them to cereblon E3 ubiquitin ligase. Current loss of signal ("down") assays identifying degraders often exhibit poor signal-to-noise ratios, narrow dynamic...
Abstract Metal‐catalyzed isomerization of N ‐ and O ‐allylic systems is emerging as an effective method to form synthetically useful iminium oxocarbenium intermediates. In the presence tethered nucleophiles, several recent examples illuminate this approach a powerful strategy for synthesis structurally complex diverse heterocycles. Concept article, we attempt cover area research through selection versatile examples.
Apoptotic induction mechanisms are of crucial importance for the general homeostasis multicellular organisms. In cancer apoptotic pathways downregulated, which, at least partly, is due to an abundance inhibitors apoptosis proteins (IAPs) that block cascade by deactivating proteolytic caspases. The Smac protein has antagonistic effect on IAPs, thus providing structural clues synthesis new pro-apoptotic compounds. Herein, we report a solid-phase approach Smac-derived tetrapeptide libraries. On...
Complexity-generating tandem Petasis 3-component/intramolecular Diels–Alder and ROM–RCM reactions for the diastereoselective synthesis of sp<sup>3</sup>-rich heterocyclic compound libraries are presented.
The nuclear SET domain containing protein (NSD) family of histone methyltransferases is an oncogenic proteins, whose overexpression directly involved in cancers, such as acute lymphoblastic leukemia (ALL) and breast cancer. NSD consists three proteins NSD1, NSD2 NSD3. These are responsible for the methylation multiple lysine residues histones, a post‐translational modification implicated transcription‐activating cell survival mechanisms DNA damage responses. particular high‐profile target...
Abstract Review: 38 refs.