494764-44-2Relevant academic research and scientific papers
Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function
Luo, Mai,Spradlin, Jessica N.,Boike, Lydia,Tong, Bingqi,Brittain, Scott M.,McKenna, Jeffrey M.,Tallarico, John A.,Schirle, Markus,Maimone, Thomas J.,Nomura, Daniel K.
, p. 559 - 15,566 (2021)
The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation—a powerful therapeutic modality within modern-day drug discovery. Using activity-based protein profiling-enabled covalent ligand-screening approaches, here we report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets, such as BRD4 and BCR-ABL, in cells. The identification of simple and easily manipulated drug-like scaffolds that can mimic the function of a complex natural product is beneficial in further expanding the toolbox of E3 ligase recruiters, an area of great importance in drug discovery and chemical biology.
Kinetic Study of the Homolytic Brominolysis of 1,2-Diarylcyclopropanes
Applequist, Douglas E.,Gdanski, Rick D.
, p. 2502 - 2510 (2007/10/02)
The rate constants for the photolytic brominolysis of 22 trans-1,2-diarylcyclopropanes in carbon disulfide relative to an internal standard, p-chlorotoluene, have been determined.The products of the brominolysis are 1,3-dibromo-1,3-diarylpropanes.The rate constants range over 5 orders of magnitude, being enhanced by electrondonating substituents on one or both benzene rings.The quantitative size of the substituent effect (ρ) at either involved carbon center is a function of the substituent at the other center.This fact suggests a continuum of transition-state structures with varying degrees of bond breaking and charge separation.
