System for Living ROMP of a Paramagnetic FeCl-Based Ionic Liquid Monomer: Direct Synthesis of Magnetically Responsive Block Copolymers.

Direct, living ring-opening metathesis polymerization of a highly paramagnetic, norbornene-based imidazolium FeCl ionic liquid monomer was achieved using the Grubbs third-generation catalyst and starting the polymerization off with an uncharged, nonparamagnetic norbornene monomer in a sequential block copolymerization. Preparing the paramagnetic norbornene imidazolium FeCl monomer in high purity was found to be crucial for enabling living polymerization behavior and generating paramagnetic diblock copolymers with predictable block lengths and compositions.

Water-soluble PDE4 inhibitors for the treatment of dry eye.

PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.

Alpha-mercaptoketone based histone deacetylase inhibitors.

In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.

Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitor.

We report the identification of KD5170, a potent mercaptoketone-based Class I and II-histone deacetylase inhibitor that demonstrates broad spectrum cytotoxic activity against a range of human tumor-derived cell lines. KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v.

KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo.

Histone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn2+ in the active site of HDACs.