Cannabinoid Receptor Meditating Compounds for Metabolic Disease

There is evidence that the metabolic effects of endocannabinoids are mediated by CB1 receptors in peripheral tissues. While prior attempts at generating CB1 receptor blockers have had serious neuropsychiatric side effects, inventors at NIH have discovered compounds that block CB1 receptors with reduced brain penetrance. In addition, some of these compounds also have a direct inhibitory effect on inducible nitric oxide synthase (iNOS), whereas another group of the compounds directly activates AMP kinas.

Treatment for Wolfram Syndrome and Other Endoplasmic Reticulum Stress Disorders with Endoplasmic Reticulum Calcium Modulators

This technology includes the use of JTV-519 and oxidized form of JTV-519, as a novel treatment for Wolfram syndrome and other diseases associated with endoplasmic reticulum (ER). JTV-519 can prevent the leakage of ER calcium to the cytosol and abnormal activation of a pro-apoptotic enzyme, calpain 2, in cell models of Wolfram syndrome. Further, these compounds can prevent cell death in beta cell models of these diseases.

Novel Human Islet Amyloid Polypeptides as Alzheimer’s Disease Biomarkers and Inhibitors of Amyloid Formation

Over 34 million Americans are living with diabetes. An estimated 6.5 million Americans are living with Alzheimer’s disease (AD) and type 2 diabetes mellites (T2DM). Amyloidosis due to aggregation of amyloid-β is key pathogenic event in AD, whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islet leads to β-cell dysfunction. A hallmark feature of T2DM is the accumulation of islet amyloid polypeptide fibrils in pancreatic islets. Such accumulations form amyloid plaques and cause apoptosis of -cells of islets. 

Novel Human Insulin Cα-Peptide as an Antagonist for Islet and Brain Amyloidosis

Over 32 million Americans are living with Diabetes and newly diagnosed cases of type 1 and type 2 diabetes is increasing. A defining feature of type 2 diabetes mellitus (T2DM) is the accumulation of islet amyloid polypeptide (IAPP) fibrils in pancreatic islets. Such accumulations form amyloid plaques, referred to as islet amyloidosis. Mounting evidence suggests that islet amyloidosis plays a causative role in the development and progression of ß-cell dysfunction in T2DM.

Methods of making and using dopamine receptor selective antagonists/partial agonists

Dopamine is a major neurotransmitter in the central nervous system and among other functions is directly related to the rewarding effects of drugs of abuse.  Dopamine signaling is mediated by D1, D2, D3, D4 and D5 receptors.  The dopamine D3 receptor is a known target to treat a variety of neuropsychiatric disorders, including substance use disorders (e.g. cocaine and opioid), schizophrenia and depression.

Analogues of Modafinil for treating sleep and attention disorders

Modafinil has attracted attention for the treatment of cognitive dysfunction in disorders such as attention-deficit/hyperactivity disorder (ADHD) as well as cocaine and methamphetamine dependence.  However, modafinil has relatively low affinity for binding to the dopamine transporter (DAT) to block dopamine reuptake, and is water-insoluble, thus requiring large doses to achieve pharmacological effects.

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.

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