Conformational Restriction of Cyanine Fluorophores in Far-Red and Near-IR Range

Small molecule fluorescent probes are important tools in diagnostic medicine. Existing far-red and near-IR cyanine fluorophores (e.g. Cy5, Alexa 647, Cy7, ICG) are active in the far-red and near-range, but these agents suffer from modest quantum yields (brightness) which limit wide utility. It has been reported that the limited brightness of these fluorophores is due to an excited-state C-C rotation pathway.

A New Class of Stable Heptamethine Cyanine Fluorophores and Biomedical Applications Thereof

Heptamethine cyanines are among the most widely used near-IR fluorophores. The near-IR range (between about 650 nm and 900 nm) is very useful for imaging applications due to the absence of background autofluorescence. Despite extensive use, many of these fluorophores suffer from chemical instability. Specifically, most of the current and commonly used fluorophores undergo a phenoxy to thiol exchange reaction in the presence of primary thiols. This exchange reaction is problematic during conjugation reactions of cysteine containing macromolecules.

Thalidomide Analogs that Inhibit Inflammation and Angiogenesis

Thalidomide and its close analogs (lenalidomide and pomalidomide) are widely used to treat a variety of diseases, such as multiple myeloma and other cancers as well as the symptoms of several inflammatory disorders. However, thalidomide is known for its teratogenic adverse effects when first clinically introduced in the 1950s, and is associated with drowsiness and peripheral neuropathy. Hence, there is intense interest to synthesize, identify and develop safer analogs. 

Small Molecule Ephrin (Eph) Tyrosine Kinase Inhibitors for the Treatment of Colorectal Cancer and Other Eph Growth-dependent Solid Tumors

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

Rapid Methods for Human Artificial Chromosome (HAC) Formation

Gene therapy is a promising strategy to treat a wide range of human diseases, and several gene therapy vectors have been developed to deliver these novel treatments. However,  risks and challenges of using these vectors remain, such as: gene integration, potential infection, immune response and maintaining long term, stable gene expression. Human artificial chromosomes (HACs) provide a unique opportunity to develop a new generation of nonviral vectors for therapeutic use as gene expression and delivery systems.