Fluorinated MU-Opioid Receptor Agonists

Summary: 
Investigators at the National Institute on Drug Abuse seek co-development partners and/or licensees for collection of mu opioid receptor (MOR) agonists as alternatives for existing compounds.

Description of Technology: 
Although existing opioids are excellent analgesics and useful as positron emission tomography (PET) radiotracers, they come with debilitating side effects. These include addiction, respiratory distress, hyperalgesia, and constipation. Therefore, there is a need for alternatives with lower adverse effects.

Intralipid as a Contrast Agent to Enhance Subsurface Blood Flow Imaging

This technology includes a blood flow imaging method that allows for a higher density of smaller particles to be detected. Current imaging methods that are based on Doppler measurements are limited by the discontinuity in the capillary flow in the space between red blood cells. The core technology is to use a scattering agent to enhance capillary flow or microcirculation. This technology has been tested for optical coherence Doppler tomography, but can be expended to any Doppler based flow imaging techniques such as laser speckle imaging.

P2Y14 Receptor Antagonists for the Treatment of Inflammatory Diseases, Including Pulmonary and Renal Conditions and Chronic Pain

This technology includes the development of selective P2Y14R antagonists for the treatment of asthma, sterile inflammation of the kidney, diabetes, and neurodegeneration. The P2Y14 receptor (P2Y14R) is a target for the treatment of inflammatory diseases, including pulmonary and renal conditions. Selective P2Y14R antagonists have demonstrated efficacy in animal models of asthma, pain, diabetes, and acute kidney injury. However, the prototypical antagonist is not optimal for in vivo administration, as it displays a low oral bioavailability.

Selective A3 Adenosine Receptor Agonists for the Treatment of Chronic Neuropathic Pain and Other Conditions

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases.

Nanobody–Antiviral Peptide Conjugates for Potent HIV Entry Inhibition

This technology includes a new class of nanobody–antiviral peptide conjugates that block HIV from infecting human CD4⁺ T-cells, positioning them for future therapeutic and prophylactic use. Nanobodies—single-domain antibody fragments—guide the drug to the virus’s docking site and impede receptor binding, while the linked peptide halts the membrane-fusion step, creating a one-two punch against viral entry.

Discovery of potent and selective D3 antagonist with alleviated hERG liability and optimized pharmacokinetic properties

One of the most challenging hurdles in creating safe and effective new medicines for many diseases is finding drugs that are effective without causing off-target cardiac issues, such as cardiac arrythmias. In collaboration with NIDA, scientists at NCATS have developed a series of novel and highly specific dopamine D3 receptor agonists and antagonists that have potential to target and treat Parkinson’s disease, Schizophrenia, Depression, and substance-use disorders including opioid addiction.

Angubindin-1 Peptide for Transient Blood-Brain Barrier Opening to Boost Chemotherapy in Malignant Glioma

This technology includes a first-in-class synthetic peptide, angubindin-1, designed to temporarily relax the blood-brain barrier (BBB)—the tightly sealed network of brain blood vessel cells that normally blocks most drugs—from the inside. By binding the tricellular tight-junction protein angulin-1/LSR, the peptide creates a reversible “molecular doorway” that lets cancer medicines such as liposomal doxorubicin (Doxil®) reach tumors in the central nervous system (CNS).

Zip14-AAV Genetic MRI Reporter System for Non-Invasive Cell & Gene-Therapy Tracking

This technology includes a gene-based magnetic resonance imaging (MRI) reporter platform that harnesses adeno-associated virus (AAV) delivery of the metal transporter Zip14 to create image contrast wherever the gene is expressed. By driving Zip14 from cell-specific promoters, investigators obtain robust, long-lasting signal changes on standard clinical MRI sequences (e.g., MPRAGE and GRE), enabling real-time visualization of living cells and their gene-expression patterns.