A new class of SHIP1 agonists that offer the potential for the development of new treatments for a variety of diseases.
Background:
An agonist is a drug or substance that binds to a cell receptor, producing the same action as the substance that would naturally bind to the receptor. Agonists form the basis for a wide variety of therapeutics. The SH-2 containing inositol 5’ polyphosphatase 1 (SHIP1) is a multifunctional protein expressed predominantly by hematopoietic cells. Over the last decade, SHIP1 has been identified as a therapeutic target due to its role in immune cells. It also plays a role in the survival of certain cancers. For example, a SHIP1-selective inhibitor has been shown to be an effective promoter of immune responses to tumor cells, a chemotherapeutic for Blymphoid cancers, hematopoietic stem cell (HSC) mobilization, and engraftment of autologous and allogeneic HSC in murine models of disease or transplantation.
Technology Overview:
This technology consists of analogs to K306, the most potent SHIP1 agonist identified to date. K306 exhibits selectivity for SHIP1 vs. the paralog enzyme SHIP2; this activation does not require the C2 domain of SHIP1 (which other known SHIP1 agonists require). Thus, K306 represents a new class of SHIP1 agonists with a novel mode of agonism. K306 can also suppress induction of inflammatory cytokines and iNOS in macrophages or microglia, but not by their SHIP1-deficient counterparts. In addition, K306 reduces TNF-α production in vivo in an LPS-induced endotoxemia assay. Finally, K306 enhances phagolysosomal degradation of synaptosomes and dead neurons by microglia, revealing a novel function for SHIP1 that might be exploited therapeutically in dementia.
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Advantages:
• Represents a new class of SHIP1 agonists with a novel mode of agonism.
• Suppresses induction of inflammatory cytokines and iNOS in macrophages or microglia.
• Reduces TNF-α production in vivo in an LPS-induced endotoxemia assay.
• Offers a potential treatment for dementia.
Applications:
The primary application for this technology is the development of therapeutics based on SHIP1 agonists.
Intellectual Property Summary:
Patent application filed on 11/15/22: 63/425,601
Stage of Development:
TRL 3 - Experimental proof of concept
Licensing Status:
This technology is available for licensing.
Licensing Potential: This technology would be of interest to anyone involved in medical research and development, including:
• Pharmaceutical and healthcare companies.
• Hospitals.
• Universities.
• Medical research laboratories.</RSS.LicensingPotential
A novel class of drugs for treating various cancers and Vitamin B12 deficiency.
Background:
Cancer is a leading cause of mortality, resulting in over 8 million deaths worldwide. Furthermore, the incidence is expected to rise by more than 50% over the next 15 years to 22 million patients and accounts for over $156 billion in yearly healthcare costs. Although treatments have dramatically improved over the past several decades, many patients are still left without a viable treatment option.
Vitamin B12 (cobalamin, CBL) is essential for cellular proliferation and interest in oncology. Research has shown its functions are crucial within tumor cells for their growth, proliferation, and migration; hence elucidating the importance of tumor cells for cobalamin is essential, while the inhibition of B12 uptake in vitro has anti-proliferating effects. In addition to the high B12 needs and uptake by cancer cells, the link between cobalamin and neoplasms also involves B12-binding proteins called transcobalamin. Hence, drugs targeting transcobalamin may be a new potential treatment for cancer.
Technology Overview:
Researchers at SUNY Downstate have developed a novel class of peptides that selectively attenuate the uptake of cobalamin into cancer cells via transcobalamin. Through several preclinical studies within the laboratory, the inventors showed their peptides could bind to the cancer cells, leading to uptake and subsequent targeted inhibition of transcobalamin in various human cancer cell lines. The inventors believe that inhibiting this critical pathway for growth may reduce tumor growth and migration. Hence, further development of this technology could become a viable class of drugs for several cancers for which cobalamin is driving growth and metastasis.
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Advantages:
Although new immunotherapies and cellular therapies are changing the paradigm of cancer treatment, they are still limited to small populations of patients. However, this technology is a novel class of potential drugs that can target a significant metabolic pathway involved in cancer, thereby improving the treatment outcomes alone or in combination with leading therapies. In addition, it may also treat Vitamin B12 deficiency which affects about 6% of those younger than 60 and over 20% of the elderly.
Applications:
Cancer and cobalamin deficiency.
Intellectual Property Summary:
Issued patent: 8,524,454 (2007)
Stage of Development:
Preclinical proof of concept.
Licensing Status:
Available for license. SUNY Research Foundation is seeking a commercial partner for licensing and/or collaborative (sponsored) research activities in this area.
The solution to the problem was a double layered cathode that includes a conductive layer serves as a cathodic current collector and an adsorptive layer.
During charging, the oxidation of I- takes place at the interface between the conductive layer and the adsorptive layer. I- in the solution transfer electrons to the conductive layer and spontaneously form adsorbed I3- ions at the absorptive layer interface. Adsorbed I3- ions can diffuse into the bulk structure of the adsorptive layer following the concentration gradient and reexpose the adsorptive layer/conductive layer interface to collect newly formed I3- ions.
During discharge, adsorbed I3- ions will be reduced to I- ions at the interface between the conductive layer and the adsorptive layer.
So the presence of an adsorptive layer can suppress I3- shuttling and improve Coulombic efficiency without changing battery capacity.
In a proof of concept experiement, carbon cloth can be used as the conductive layer, while the adsorptive layer can be any of a number of materials including conducting polymers such as polypyrrole (PPy), polyaniline (PANi), and poly(3,4-ethylenedioxythiophene) (PEDOT) as well as metallic comipounds.
Platinum oxide nanoparticles of approximately 2 nm in diameter are deposited on carbon nitride (C3N4) nanosheets by thermal refluxing of C3N4 and PtCl2 or PtCl4 in water. These nanoparticles exhibit apparent electrocatalytic activity toward the hydrogen evolution reaction (HER) in acid. Interestingly, the HER activity increases with increasing Pt4+ concentration in the nanoparticles, and the optimized catalyst even outperforms commercial Pt/C, exhibiting an overpotential of only −7.7 mV to reach the current density of 10 mA cm−2 and a Tafel slope of −26.3 mV dec−1.
Field-portable cost-effective platform for high-throughput quantification of particulate matter (PM) using computational lens-free microscopy and machine-learning
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Dehydrogenation of alkane with developed catalyst.â
Invention Summary:
Olefins (alkenes) are key intermediates in the production of fuels and many commodity chemicals. Alkanes, and particularly light linear alkanes, are increasingly abundant but of limited value. The dehydrogenation of alkanes is therefore an economically very attractive route to olefins.
Researchers at Rutgers University have developed highly effective and regioselective catalysts for the dehydrogenation of n-alkanes. The developed catalysts result in high turnover numbers, >1000 TO, and are particularly effective for the acceptor-less dehydrogenation of nâalkanes, in which no sacrificial acceptor is required and the only by-product is dihydrogen. The reaction rate under typical conditions was found to be limited by the rate of expulsion of dihydrogen from a simple reaction vessel in which reflux of the solution provided the driving force for H2 expulsion.
Advantages:
- Highly effective and non-obvious catalyst for alkane dehydrogenation
- Convenient synthesis
Market Applications:
- Chemical intermediate manufacturing
- Petrochemical industry
- Automobile
Intellectual Property & Development Status: US Patent US 2021/0291154-A1. Available for licensing and/or research collaboration. Please contact marketingbd@research.rutgers.edu
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The Phebox ligand
Invention Summary:
Phebox ligands are organic complexes useful for a number of catalytic transformations of other organic molecules, including transformations of alkanes generally requiring harsh conditions. Since catalytic transformations using this class of ligands intrinsically involve the activation of C-H bonds, the degradation of the phebox ligand via reactions of the C-H bonds of the aryl position (benzylic or aryl C-H bonds) is potentially problematic.
Rutgers researchers have developed the bis-CF3-Phebox ligand and its non-obvious preparation method. The ligand can be complexed with metals to yield stable, convenient-to-synthesize, and highly effective catalysts. Therefore, the aryl positions can be protected with -CF3 groups. A multi-step synthesis of bis-CF3-Phebox has been successfully achieved and the bis-CF3-Phebox was used as an iridium complex in the alkane dehydrogenation of n-decane and n-dodecane with high catalytic turnover numbers.
Advantages:
- Novel, highly effective, and non-obvious catalyst for alkane dehydrogenation
- Novel and convenient synthesis to the catalyst.
Market Applications:
- Conversion of low-value alkanes to high-value alkenes
- Intermediates in catalytic cycles for further reactions of the olefins
- Conversion of alkanes to other unsaturated high-value products such as aldehydes, alcohols, polymers, and aromatics.
Intellectual Property & Development Status: US Patent US 2021/0300910-A1. Available for licensing and/or research collaboration. Please contact:
marketingbd@research.rutgers.edu
Block Diagram of Laboratory Radiocarbon analyzer
Invention Summary:
Drug metabolism studies require highly sensitive radiocarbon (C14) detection. Accelerator mass spectrometry (AMS) is a gold standard method for drug metabolism and related studies, but the high cost, low speed, complexity and large footprint of AMS instruments prohibits on-site testing. While liquid scintillation counters have a more compact footprint, they do not provide the necessary sensitivity for many drug studies.
Researchers at Rutgers have developed a low-cost, benchtop, laser-based system for quantification of C14. Using the optogalvanic effect (OGE), it is possible to detect C14 at concentrations as low as one part per trillion. Recent developments have led to new electronic circuitry and new calibration algorithms that further increase the sensitivity and stability of this optogalvanic spectroscopy method. These improvements have greatly improved both reproducibility and dynamic range.
This system will enable more rapid, inexpensive, and sensitive testing of radiocarbon, leading to acceleration of the drug development process.
Similar Technology:
https://techfinder.rutgers.edu/tech/Optogalvanic_Effect_Detection_System
Market Applications:
- Carbon-14 detection
- Drug development
- Carbon dating
- Environmental monitoring
Advantages:
- Small samples ~ 10µg
- High sensitivity (1 part per trillion)
- Low cost and high speed
- Easy to use benchtop system
- Large dynamic range
\r\n\r\nUW Madison researchers have developed a novel way to manufacture large amount of micellular paclitaxel. Rather than using organic solvents to get the paclitaxel solubilized and loaded into micelles, the researchers added polyethylene glycol (PEG) to the PEG/PGA polymer and paclitaxel. The mixture was heated to 60°C to obtain a transparent liquid which was vortexed to ensure homogeneity followed by keeping the solution at 60°C for 30 min. The solution was then kept at 60°C or cooled down to 40 or 25°C and hydrated by addition of DI water with the same temperature as the solution and employing either rapid, slow or no mixing (diffusion) to form the micelles. The loaded micelles can be freeze dried without the removal of excess PEG. It can then be stored stably and rehydrated when needed.
The inventors have tried PEG at various molecular weights at a weight ratio of 1:2:40 w/w/w drug/copolymer/PEG. Using PEG at 1000 molecular weight provided the best drug loading properties but also the largest micelles. The inventors found that cooling the mixture to 40°C and then diluting with water provided a better drug loading efficiency than adding the water at 60°C.
IP Status: Research Tool
Applications
- In vitro cell culture
- Drug development
Key Benefits & Differentiators
- Derived from mouse models with DUX4 gene conformation appropriate for drug testing
Technology Overview
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent hereditary muscle disorders. The DUX4 gene encodes a protein that is expressed in FSHD but not in healthy muscle cells. This inappropriate expression initiates a gene deregulation cascade causing differentiation defects, muscle atrophy, and oxidative stress. To test potential drug candidates, appropriate research tools (e.g. cell lines) are needed.
Researchers at the University of Minnesota have developed primary skeletal muscle cell lines isolated from DUX4 expressing FSHD mice. These myoblast and fibroblast cell lines are appropriate for testing potential drug candidates against DUX4 protein.
Technical Information
Primary mouse myoblasts from iDUX4pA mouse model (2019-199)
Organism: Mus musculus, mouse
Tissue: Skeletal Muscle
Cell Type: Myoblasts
Disease: Facioscapulohumeral muscular dystrophy (FSHD)
Applications: These primary adherent cells are grown in culture to model DUX4 myopathy. Suitable for in vitro testing of drug candidates and mechanistic studies.
Product format: Frozen
Description: Primary myoblasts isolated from the skeletal muscle of FSHD mouse model described in Dandapat, A. et al. (2014). Cell Rep. 8(5):1484-96.
Primary mouse fibroblasts from iDUX4pA mouse model (2019-199)
Organism: Mus musculus, mouse
Tissue: Skeletal Muscle
Cell Type: Fibroblast
Disease: Facioscapulohumeral muscular dystrophy (FSHD)
Applications: These primary adherent cells are grown in culture to model DUX4 myopathy. Suitable for in vitro testing of drug candidates and mechanistic studies.
Product format: Frozen
Description: Primary fibroblasts isolated from the skeletal muscle of FSHD mouse model described in Dandapat, A. et al. (2014). Cell Rep. 8(5):1484-96.
Phase of Development
Cell lines have been established and characterized.
Desired Partnerships
This technology is now available for:
- License
- Sponsored research
- Co-development
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