Targeting the spliceosome with small molecule inhibitors provides a new avenue to target cancer by intercepting alternate splicing pathways. Although our understanding of alternate mRNA splicing remains poorly understood, it provides an escape pathway for many cancers resistant to current therapeutics. These findings have encouraged recent academic and industrial efforts to develop natural product spliceosome inhibitors, including FD-895 (1a), pladienolide B (1b), and pladienolide D (1c), into next-generation anticancer drugs. The present study describes the application of semisynthesis and total synthesis to reveal key structure-activity relationships for the spliceosome inhibition by 1a. This information is applied to deliver new analogs with improved stability and potent activity at inhibiting splicing in patient derived cell lines.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809018 | PMC |
| http://dx.doi.org/10.1021/jm400861t | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
"Elegy of blossoms": Decrypting the dynamics of petal senescence in L.
Physiol Mol Biol Plants
December 2024
Department of Botany, University of Kashmir, Srinagar, 190006 India.
Petal senescence represents a crucial phase in the developmental continuum of flowers, ensuing tissue differentiation and petal maturation, yet anteceding seed formation and development. Instigation of petal senescence entails myriad of changes at the cytological, physiological and molecular dimensions, mirroring the quintessential characteristics of cell death. In the current investigation biochemical and molecular intricacies were scrutinized across various developmental stages (bud to the senescent phase).
View Article and Find Full Text PDFUnraveling the Cleavage Reaction of Hydroxylamines with Cyclopropenones Considering Biocompatibility.
J Am Chem Soc
December 2024
Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, The Institute of Molecular Medicine Medicine, Wuhan University People's Hospital, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, Hubei 430072, China.
We develop a latent biocompatible cleavage reaction involving the hitherto unexplored interaction between hydroxylamines and cyclopropenones. Our study addresses the regioselectivity challenges commonly observed in asymmetric cyclopropenone transformations, substantiated by variations in substrate, Density Functional Theory calculations, and NMR analysis. This reaction is characterized by high efficiency, broad substrate scope, stability, latent biocompatibility, and mild reaction conditions.
View Article and Find Full Text PDFPhotocatalytic 1,3-oxyheteroarylation of aryl cyclopropanes with azine -oxides.
Chem Sci
December 2024
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Korea
Cyclopropanes, valuable C3 building blocks in organic synthesis, possess high strain energy and inherent stability. We present an efficient, environmentally benign 1,3-oxyheteroarylation of aryl cyclopropanes using azine -oxides as bifunctional reagents under visible light irradiation. This metal-free method yields β-pyridyl ketones under mild conditions.
View Article and Find Full Text PDFCiprofol versus propofol for anesthesia induction in cardiac surgery: a randomized double-blind controlled clinical trial.
BMC Anesthesiol
November 2024
Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Background: Ciprofol, a novel intravenous general anesthetic with a chemical structure similar to propofol, exhibits significantly enhanced potency. It offers a rapid onset, reduced incidence of injection pain, and has comparable effects on heart rate and blood pressure to propofol. However, clinical data on its use for anesthesia induction in cardiac surgery remain limited.
View Article and Find Full Text PDFA High-Voltage n-type Organic Cathode Materials Enabled by Tetraalkylammonium Complexing Agents for Aqueous Zinc-Ion Batteries.
Adv Mater
December 2024
Department of Chemistry & Biochemistry, The Ohio State University, 100 West 18th Avenue Columbus, Ohio, 43210, USA.
Article Synopsis
- Tetrabutylammonium (TBA) salt of hexacyano-substituted cyclopropane dianion (Cp(CN) ) is developed using a simple two-step method and shows promise as a high-voltage n-type organic cathode for aqueous zinc-ion batteries (AZIBs).
- Adding tetrabutylammonium triflate (TBAOTf) to the electrolyte helps reduce dissolution problems, improving the battery's cycling stability.
- The Cp(CN) cathode achieves a high discharge voltage of 1.43 V and maintains 85% capacity after 1000 cycles, demonstrating its potential effectiveness in energy storage applications through a reversible two-electron redox process.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!