DESCRIPTION (provided by applicant): Neurodegenerative disease represents a major challenge to the maintenance of health and quality of life in diverse segments of the population. Among the various diseases of this class, Parkinson's disease (PD) is a major cause of morbidity and diminished life… More

DESCRIPTION (provided by applicant): 0steoporosis represents a major challenge to the maintenance of health and quality of life in an aging population. Among the most promising and least exploited therapeutic interventions are those treatments designed to increase bone density. The selection and… More

DESCRIPTION (provided by applicant): Myopathy (muscle atrophy, or muscle wasting) is a serious clinical complication of cancer, HIV/AIDS, diabetes, and other chronic diseases, leading to increased morbidity and reduced life expectancy. While symptoms have been addressed by a number of interventions,… More

DESCRIPTION (provided by applicant): A key aspect of cellular regulation that affords a number of potential opportunities for pharmacological intervention is the maintenance of protein homeostasis. Proteins are continuously being synthesized and degraded in cells, and their cellular levels must be… More

DESCRIPTION (provided by applicant): VDU1 is a recently described ubiquitin isopeptidase that binds to and is ubiquitinated by the E3 ligase complex of the vonHippel-Lindau protein (pVHL). VDU1 has been found to be a target of ubiquitination (and proteasomal degradation) by the tumor suppressor… More

DESCRIPTION (provided by applicant): Rheumatoid arthritis (RA) is associated with chronic inflammation and overgrowth of synovial cells, and factors involved in these processes are potential targets for discovery of therapeutic drugs. Hrd1, also known as synoviolin, is an E3 ubiquitin ligase enzyme… More

DESCRIPTION (provided by applicant): Muscle atrophy (wasting) is a serious clinical complication of diabetes and other chronic pathoses, leading to increased morbidity and reduced life expectancy. While symptoms have been addressed by a number of interventions, no successful therapy has been… More

DESCRIPTION (provided by applicant): a-TrCP is a recently identified component of the SCF ubiquitin E3 ligase that purportedly targets multiple proteins for ubiquitination and degradation. Some of the demonstrated targets, such as I-?B and a-catenin, are members of signal transduction pathways that… More

DESCRIPTION (provided by applicant): Osteoporosis remains a major challenge to the maintenance of health and quality of life in an aging population. Among the most promising and least exploited therapeutic interventions are those treatments designed to inc rease bone density. The selection and… More

DESCRIPTION (provided by applicant): AMSH is a recently described ubiquitin isopeptidase that is associated with endosomal trafficking of the human epithelial growth factor receptor (EGFR). The ubiquitin pathway is closely involved in the signal transducti on and trafficking mechanisms that regulate… More

DESCRIPTION (provided by applicant): Because of its involvement in a broad range of cellular signal transduction and other mechanisms, the ubiquitin pathway is now recognized as a new opportunity for discovering drugs to treat a variety of diseases. Initia l success was achieved with the approval of… More

DESCRIPTION (provided by applicant): Mutations in the ubiquitin E3 ligase component pVHL are observed in 100% of patients with the autosomal dominant von Hippel-Lindau disease (VHL) and predisposes individuals to a variety of tumors including clear cell ca rcinomas of the kidneys. Furthermore,… More

DESCRIPTION (provided by applicant): Salmonella contamination of food products, caused by Salmonella enterica, which infects humans, cattle, and poultry, is a serious public health problem, resulting in product recalls and illness. Moreover, Salmonella has been used successfully as a bioterrorism… More

DESCRIPTION (provided by applicant): The one or two osteoporosis drugs now available that build new bone rather than simply prevent further bone loss are not without issues, and the market for anabolic therapy remains open. Progenra, a ubiquitin based drug discovery company, is currently seeking… More

DESCRIPTION (provided by applicant): Various ubiquitin and ubiquitin-like protein pathway enzymes have been shown by biochemical and genetic evidence to be involved in disease states and are thus regarded as molecular targets for drug discovery. Regarding neoplastic disease, for example, certain… More

DESCRIPTION (provided by applicant): As the prominence of the ubiquitin and ubiquitin-like pathways increases, the need for assays to measure the activity of the enzymes involved in these pathways grows. Currently the only high throughput methods for meas uring ubiquitin and ubiquitin-like… More

DESCRIPTION (provided by applicant): Aberrant overactivation of WNT signaling appears to play a major role in Idiopathic Pulmonary Fibrosis (IPF). Inhibitors of overactivated WNT signaling are candidates for therapy of IPF. USP34, a novel de-ubiquitylating enzyme, has been identified as an IPF… More

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus (T2D) has an enormous physical and economic impact worldwide. Despite current treatments, T2D often ultimately requires insulin replacement therapy and diminishes the patients' quality of life o wing to complications associated with… More

DESCRIPTION (provided by applicant): With the approval of the proteasome inhibitor Velcade for multiple myeloma therapy, the ubiquitin pathway has been validated for drug discovery. An alternative ubiquitin-associated degradation pathway is lysosomal; for example, the ubiquitin E3 ligase Cbl… More

DESCRIPTION (provided by applicant): Hypercholesterolemia is a major factor in cardiovascular disease. In the USA, more than 35 million individuals have high total cholesterol and thus twice the normal risk of heart disease. The LDL receptor (LDLR) is critical to cholesterol regulation, as mutation… More

DESCRIPTION (provided by applicant): As in the past, most new FDA-approved drugs for cancer and other indications are derived from natural products or inspired by natural products. Accordingly, it is proposed here to screen the NCI collection of extracts to discover novel molecules that inhibit the… More

DESCRIPTION (provided by applicant): Because of its involvement in a broad range of cellular signal transduction and other mechanisms, the ubiquitin pathway is now recognized as a new opportunity for discovering drugs to treat a variety of diseases. Initial success was achieved with the approval of… More

DESCRIPTION (provided by applicant): Approximately 70,000 individuals worldwide suffer from the debilitating disease cystic fibrosis (CF), which typically is fatal owing to sepsis in the abnormally viscous mucus of the lung. Various treatments are employed to address symptoms, but an approved drug… More