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Siderophore-Based Immunization Against Gram-Negative Bacteria

Bacterial pathogens such as E. coli and Salmonella hijack the host’s iron to cause infection. This invention describes an immunization strategy for triggering an immune response against the iron-sequestering agent secreted by the pathogen, thus turning the bacterial virulence mechanism against itself, and thereby resulting in host immunity.

Novel therapeutic approach for obesity: Pharmacological targeting of Kv1 potassium channels

Obesity is a global epidemic that is in need of novel and safe therapeutics. Despite the enormous efforts by pharmaceutical companies, there is a shortage for safe therapeutics for obesity. Researchers at UCI have developed a selective inhibitor of Kv1.3 potassium channel, ShK-186, which displays powerful anti-obesity effects in a mouse model of diet-induced obesity. Using critical experimental measures, researchers highlight the potential use of Kv1.3 blockers in the treatment of obesity and insulin resistance.

Thrombospondins as a target to treat neuropathic pain

Neuropathic pain is a common problem, though, there are few existing pain medications have specific targets to treat this type of pain, and often lack efficacy and tolerance. The invention identifies specific proteins and related genes as targets for treating neuropathic pain in an animal model.

Stimuli Responsive Immunostimulants

An immune response typically occurs during inflammation, auto-immune diseases, or cancers. In such cases, chemical triggers, or immunostimulants, recognized by receptor proteins at cell membranes activate the immune cells. Researchers can use these immunostimulants to test how different cell subsets contribute to immune response mechanisms. This invention describes a novel type of immunostimulant that can be toggled on and off, both inside the body and in vitro.

Enhanced Cell/Bead Encapsulation Via Acoustic Focusing

The invention consists of a multi-channel, droplet-generating microfluidic device with a strategically placed feature. The feature vibrates in order to counteract particle-trapping micro-vortices formed in the device. Counteracting these vortices allows for single particle encapsulation in the droplets formed by the device and makes this technology a good candidate for use in single cell diagnostics and drug delivery systems.

Aptamers that promote neuronal growth by binding to and blocking the protein Nogo

Neuronal growth inhibiting protein (Nogo), blocks regrowth of damaged neuronal projections (axons) in neurodegenerative disorders. Currently, researchers are developing antibody proteins to inhibit Nogo and produce axon regrowth in a variety of disorders. However, such antibodies are unstable and costly to synthesize. At UCI, the synthesis of nucleic acid molecules called aptamers that selectively bind and block Nogo to promote axonal growth presents a promising alternative pharmaceutical target for treating a range of disorders including spinal cord injury, stroke, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS).

Chiral Polymers Of Intrinsic Microporosity For Membrane Separation Of Enantiomers

Many pharmaceutical drugs exist as enantiomeric pairs, chemically-distinct mirror image of one another that often exhibit marked differences in biological activity. Current methods for separating enantiomeric mixtures to generate pure form of an effective drug involve multiple time-consuming and expensive steps. The invention herein describes a polymer that can selectively separate enantiomers in a simple, continuous process.

microfluidic device for preparation of monodisperse microcapsules and microvesicles

Many applications, ranging from in vivo cell culture growth to drug delivery, rely on microcapsules to encapsulate and protect cells or molecules until their desired release. These microcapsules are typically generated in immiscible fluid, which must be depleted before they can be effectively used. Researchers at UCI have recently developed a paper-based microcapsule extraction technique that is quicker, cheaper, and less damaging than conventional methods.

Synthesis of Lipobactins and Teixobactin Analogues – New Antimicrobial Compositions against Gram-Positive Bacteria

With the discovery of penicillin in the 1940’s, many scientists proclaimed the defeat of infectious diseases which had plagued mankind. However, the remarkable healing power of antibiotics unfortunately invited widespread and indiscriminate use of antibiotics. This misuse and overuse of antibiotics has led to the dramatic rise in antibiotic resistant bacterial strains and increased healthcare costs.

Pyrite Shrink-Wrap Laminate As A Hydroxyl Radical Generator

The invention is a diagnostic technology, as well as a research and development tool. It is a simple, easy to operate, and effective platform for the analysis of pharmaceuticals and biological species. Specifically, this platform generates hydroxyl radicals for oxidative footprinting – a technique commonly employed in protein mapping and analysis. The platform itself is inexpenisve to fabricate, scalable, and requires nothing more than an ordinary pipet to use. In addition, it is highly amenable to scale-up, multiplexing, and automation, and so it holds promise as a high-throughput method for mapping protein structure in support of product development, validation, and regulatory approval in the protein-based therapeutics industry.

New Borylated Heterocycles: Indoles, Isoxazoles, Lactones, and Benzofurans, and the Methods to Make Them (related to UC Case 2013-921)

Boron building blocks play a key role in modern organic chemistry, especially in drug design and materials synthesis. Methods to generate heterocycles and borylated compounds in the same synthetic step are largely unknown; the ability to do both increases efficiency and rapidly builds molecular complexity while providing access to previously unavailable building blocks.

High Affinity CYP3A4 Inhibitors

Cytochrome P450 3A4 (CYP3A4) is a key metabolizing enzyme that regulates the oxidation and clearance of most drugs. The inhibition of this enzyme may be useful in improving the efficacy of drug cocktails and the ability to give lower, less toxic doses of drugs. The development of new CYP3A4 inhibitors with high affinity and specificity is described.

Novel compounds for the treatment of fungal infections

Treatment of fungal infections remains a medical challenge and better and more efficacious treatments are needed. Antifungal agents provide relief from fungal infections that can potentially infect almost any part of the human body, but, systemic fungal infections can be life threatening. A commonly prescribed antifungal drug for systemic fungal infections is fluconazole. Fluconazole tends to be well tolerated; however there have been reports of various undesirable side effects as well as the emergence of fluconazole resistant fungal strains.

Improvements of cognitive function in age-related disorders and Alzheimer's disease

Cognitive deficits associated with aging and other age-related disorders involve deficits in processing sensory information, attention, consolidation of memory, recall of information, and executive functions such as planning, problem solving and self-monitoring among others. There is a large unmet medical need to identify therapies and novel therapeutic regimes for the treatment of cognitive dysfunction, e.g., cognitive deficits related to aging, age-related disorders and Alzheimer's disease. Previously published research suggests a correlation between neurological disorders and trimethylation of histone H3K9 in the brain. Therefore, an inhibitor of histone methyl transferase SUV39h1 and its effects on the progression of age-related disorders was investigated.

CYP3A4 Epoxygenase Inhibitors for ER+ Breast Cancer Treatment

Small molecule CYP34A inhibitor oncology therapeutics are being developed in collaboration between scientists at UC Irvine and U of Minnesota. These molecules have been shown effective against ER+ xenograft models of breast cancer. Due to their mechanism of action, these molecules may enhance treatment with tamoxifen and paclitaxel to decrease risk of recurrence.

Small Molecules as chemotherapeutics agents for cancer treatment by restoring p53 function.

The tumor suppressor p53 normally functions to prohibit unregulated growth of cells. p53 is the most frequently mutated gene in human cancers. The most frequent p53 mutation is a missense mutation known as R175H. We have discovered 11 small molecules that interact with and stabilize R175H protein. The stabilization of R175H by these small molecules restores p53 function and can be a potential drug candidate. Currently, there are no known drug targets that specifically work on p53 mutants and our compounds will be the first to have specific targeting capacity.

Imprinted Polymer Nanoparticles

Synthetic polymer nanoparticles (NPs) capable of recognizing specific biomacromolecules and can be used as substitutes for natural antibodies .

Novel Chitosan Derivative as a Systemic Drug Delivery Agent and an Antibiotic Treatment

Researchers at the University of California, Irvine have developed a novel chitosan derivative that may be used simultaneously as a systemic drug delivery agent and a systemic antibiotic treatment.

Novel Inhibitors Of Endocannabinoid Inactivation for Treatment of Pain, Anxiety and Depression

Bioactive lipids, including anandamide (AEA), are important signaling molecules in humans. Acting through CB1 cannabinoid receptors in the brain and peripheral tissues, the local concentrations of these lipids have effects on several areas of human health including pain sensation, inflammation, appetite regulation, anxiety, and depression. The regulation of these lipids is partially controlled by their degradation rate by the enzyme fatty acid amide hydrolase (FAAH). The present portfolio of inventions provides novel small-molecule inhibitors FAAH, including molecules that are limited to peripheral FAAH inhibition as well as molecules improved for oral bioavailability. These compounds have been tested in a number of animal models and one molecule has entered clinical trials in humans. This portfolio includes molecules with IC50 values at single digit nanomolar and in some cases, less than 1.0 nanomolar concentrations in vitro.

Novel Acid Ceramidase Inhibitors for Oncology and Hyperproliferative Skin Disorders

Acid ceramidase (AC) catalyzes the hydrolysis of the lipid messenger ceramide thereby regulating ceramide levels in cells. AC is involved in multiple physiological and pathological processes, including cancer resistance and neuropathic pain. Previous AC inhibitors are ceramide analogs with weak inhibitory activity in vitro and virtually no utility in vivo.  The present portfolio of inventions provides two chemically distinct classes of small-molecule inhibitors of intracellular AC activity, which act at single digit nanomolar concentrations in vitro and at low doses in vivo.

Small Molecules for Analgesia and Anti-Nausea

Anandamide is a biologically active lipid molecule that regulates multiple biological functions – including pain, nausea and mood – by activating CB1 cannabinoid receptors in the brain and peripheral tissues. In the brain, the biological actions of anandamide are stopped by a selective mechanism that starts with the uptake of anandamide by neurons and glial cells. Researchers at UCI have developed novel, small molecules that inhibit this transport process, causing anandamide levels to increase. This produced in turn a spectrum of CB1 receptor-mediated responses that include reduced pain and nausea.

Potential Novel Anti-Viral Target For Chemotherapeutics Against Picornaviruses, Such As Human Rhinovirus An Entervirus 71

Picornaviruses, viruses that belong to the family Picornaviridae, are single-stranded RNA viruses that infect both humans and animals. The major picornaviruses that affect humans include enteroviral pathogens (poliovirus, coxsackievirus, enterovirus, echovirus), rhinoviruses (approximately 105 serotypes), hepatitis A virus, and parechoviruses. Currently, there no medications indicated to treat picornavirus infections, and only the symptoms can be treated. New treatments for picornavirus infections would be extremely useful for medical professionals and their patients. Researchers at the University of California, Irvine have discovered an enzyme that is involved in the virus life cycle of the picornavirus. This enzyme may be a novel anti-viral target for chemotherapeutics that can be used against picornaviruses.

New imaging agents for AB-amyloid plaques and tangles

Researchers at the University of California, Irvine have synthesized new chemical entities that selectively bind to regions in the brain that accumulate Aβ-amyloid plaques.

Chip-Based Droplet Sorting

Microfluidic devices are poised to revolutionize environmental, chemical, biological, medical and pharmaceutical detectors and diagnostics. The term “microfluidic devices” loosely describes the new generation of instruments that mix, react, count, fractionate, detect, and characterize samples in a micro-electro-mechanical system (MEMS) circuit manufactured through standard semiconductor lithography techniques. Although a wide array of microfluidic technologies are currently available, novel MEMS fluidic systems are needed as scientists continue to work with smaller sample volumes and desire devices with increased sensitivity and effectiveness. Researchers at the University of California, Irvine have developed a unique non-contact system for sorting monodisperse water-in-oil emulsion droplets in a microfluidic device. The technology can be coupled to other on-chip processes to increase device efficiency by sorting out un-reacted droplets.

New Treatment for the Prevention and Reversal of Non-Alcoholic Fatty Liver Disease (NAFLD)

Researchers at the University of California, Irvine have found a new use for a known compound for treatment of fatty liver disease which has been shown to be effective in animal studies.

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