Rational Adaptation of L3MBTL1 Inhibitors to Create Small‐Molecule Cbx7 Antagonists

Tackling EGFR signaling with TACE antagonists: a rational target for metalloprotease inhibitors in cancer.

TNF-alpha converting enzyme (TACE/ADAM17) is a transmembrane metalloprotease that plays a key role in the cleavage and mobilization of receptor ligands that are initially synthesized as membrane-tethered precursors. For many years, attention has focused on the role of TACE-dependent TNF-alpha cleavage in arthritis and, more recently, it has become apparent that TACE also plays an important role...

Rational combinations using HDAC inhibitors.

In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as histone deacetylase inhibitors (HDACi) have attracted enormous attention as anticancer drugs. In numerous in vitro and preclinical settings, the...

Thromboxane receptors antagonists and/or synthase inhibitors.

Atherothrombosis is the major cause of mortality and morbidity in Western countries. Several clinical conditions are characterized by increased incidence of cardiovascular events and enhanced thromboxane (TX)-dependent platelet activation. Enhanced TX generation may be explained by mechanisms relatively insensitive to aspirin. More potent drugs possibly overcoming aspirin efficacy may be desira...

ACE inhibitors, angiotensin receptor antagonists and bradykinin.

Rational discovery of novel nuclear hormone receptor antagonists.

Nuclear hormone receptors (NRs) are potential targets for therapeutic approaches to many clinical conditions, including cancer, diabetes, and neurological diseases. The crystal structure of the ligand binding domain of agonist-bound NRs enables the design of compounds with agonist activity. However, with the exception of the human estrogen receptor-alpha, the lack of antagonist-bound "inactive"...