A5079805788- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Advanced Proteomics Techniques and Applications
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Genomics and Chromatin Dynamics
Scripps Research Institute
2021-2025
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2023
Scripps (United States)
2023
Significance To address the unmet clinical need for effectively suppressing estrogen receptor (ER) activity with both de novo resistance and in advanced ER-positive breast cancers that are resistant to standard-of-care antiestrogens, we have developed dual-mechanism ER inhibitors (DMERIs) employ two distinct ER-targeting moieties. These DMERI elicited noncanonical structural perturbations of ligand-binding domain stabilized multiple antagonist substates within dimer generate highly...
Abstract Oligomerization of proteins and their modified forms (proteoforms) produces functional protein complexes 1,2 . Complexoforms are that consist the same set with different proteoforms 3 The ability to characterize these assemblies within cells is critical understanding molecular mechanisms involved in disease designing effective drugs. An outstanding biological question how drive function oligomerization complexoforms. However, tools define endogenous proteoform-proteoform/ligand...
Abstract Disclosure: J.C. Nwachukwu: None. J.W. Njeri: T. Venables: C. Seath: M.E. Pipkin: Y. Hou: B.S. Katzenellenbogen: J.A. K.W. Nettles: We recently developed Dual Mechanism Estrogen Receptor-α (ERα) Inhibitors (DMERI) with more antagonist efficacy than selective ERα modulators (SERMs) such as tamoxifen, and degraders (SERDs) fulvestrant in certain breast cancer models. Current models of anti-estrogen action are largely based on genomics studies growth arrested cells, where the effects...