Despite therapeutic advances, human immunodeficiency virus (HIV) is still a pervasive disease, with approximately 37 million people infected worldwide. Peptides have become popular therapeutic agents, as these proteins offer structural diversity for many different diseases. Several peptides were commercially developed as HIV therapeutics, demonstrating the high potential for peptides in treating HIV.
There are currently no methodologies that allow for epigenome, genome and transcriptome analysis all in a single cell. In addition, there are currently no methodologies that permit repeating the results of these analyses on the same single cells.
Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types. Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics. Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.
Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types. Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics. Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.
Non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to treat a variety of inflammatory conditions. Many of these conditions, such as cancer or arthritis, require long term use of the NSAIDs due to the chronic nature of the disease. However, the NSAIDs in current use have toxicities associated with their long-term use that hinder their use for these chronic conditions.
The proto-oncogene c-Myc is deregulated and overexpressed in ~70% of all cancers. Thus, c-Myc is an attractive therapeutic target since disrupting c-Myc activity could be used as pan-chemotherapy. Beyond cancer, Myc is also a positive effector of tissue inflammation, and its function has been implicated in the pathophysiology of heart failure. Because c-Myc is a transcription factor, a rationally designed small molecule targeting c-Myc would be required to exhibit significant specificity.
RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs.
Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.
Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.
Melanoma is a particularly aggressive form of cancer primarily caused by over-exposure to sunlight. Although melanoma can strike at any age, the malignancy disproportionately impacts persons of advanced age, as these individuals often have decades of repeated exposure to harmful levels of ultraviolet radiation. Scientists at NIH among others have clarified the link between advanced melanoma and other malignancies and expression of SPANX-B.