This technology includes the use of the (N)-methanocarba phosphonate analogues of 5’-AMP as cardioprotective agents for use in conditions such as cardiomyopathy and heart failure. We previously found a compound, MRS2339 (a phosphate derivative that can be slowly cleaved in vivo and lose potency), which activates the appropriate receptors and is protective in models of heart failure in several species (mouse, dog). MRS2339 is a phosphate derivative that can be slowly cleaved in vivo and lose potency. We now extend this technology to more stable derivatives, i.e.

This technology includes a sphingosine kinase 1 (Sphk1) knockout mouse model for use in developmental biology research. Sphingosine-1-phosphate (S1P) is synthesized from sphingosine and ATP by the action of sphingosine kinase, and activates cell signaling. Two sphingosine kinases, SPHK1 and SPHK2, have been identified. To study the physiological function of SPHK1, Sphki null mice were generated. The mice were viable, fertile, with no obvious abnormalities. Total SPHK activity in most tissues was substantially reduced, suggesting the presence of other sphingosine kinases.

This technology includes a mouse model for S1 pr1 to be used in development biology research. Sphingosine-1-phosphate is a potent bioactive compound that activates a family of G-protein coupled receptors known as Edg or S1P receptors. Triggering these receptors on cells may have important effects related to inflammation, immunity, cancer, angio-genesis, cell proliferation, adhesion, cardiovascular function, nervous system function and injury responses.

This technology includes a new class of oligomeric molecules called thyclotides for diagnostic and therapeutic development. Thyclotides is described where chiral tetrahydrofuran (THF) diamine units are linked together with alternating glycines, and nucleobases are attached to this backbone as sidechains. The thyclotide sequence consists of a series of nucleobases similar to that of a nucleic acid sequence. Thyclotides are easily synthesized and purified with excellent solubility in water. Thyclotide sequences bind to complementary DNA and RNA sequences with very strong affinity.

This technology includes P2X4R adenosine receptor antagonists, including NP-1815-PX and 5-BDBD, for treating stroke. Stroke is the fifth leading cause of death for Americans and a leading cause of serious long-term disability. Current approaches to treating ischemic stroke are primarily limited to the administration of thrombolytic therapeutics such as tissue plasminogen activator, or to an invasive endovascular procedure involving the use of a clot removing/retrieving device.

This technology includes polyclonal antibodies against MLL3 (KMT2C), MLL4, PA1, UTX And PTIP for the development of treatments for development diseases and cancer. Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear.

This technology includes a novel family of adenosine kinase (AdK) inhibitors, including pharmaceutical compositions containing the adenosine kinase inhibitors, and their use for preventing epilepsy and its progression in patients. Endogenous adenosine (i.e., naturally occurring adenosine) acts on G protein-coupled receptors (adenosine receptors, ARs) in the central nervous system to suppress seizures and pain, and to blunt the effects of ischemia (a restriction in blood supply to tissues).

This technology includes an oral treatment for HIV infection. Nipamovir is a low molecular weight mercaptobenzamide derivative that is simple to produce on kilogram scale and which can be used to lower or eliminate the infectivity of HIV. Extended treatment of Simian immunodeficiency virus (SIV)-infected macaques with Nipamovir lowers the viral load by 1 log unit, and eliminates the ability of remaining virus to infect other cells. Nipamovir shows similar antiviral activity in HIV-infected human cells. There are no toxic side-effects observed in animal studies with Nipamovir.

This technology includes PPTN which can be used to study treatments of inflammatory diseases. PPTN is currently a useful pharmacological probe that many labs in the field of purinergic signaling are interested in obtaining. The availability of PPTN as a research tool will stimulate basic advances in the field and possibly eventually lead to new treatments. However, PPTN itself is unsuitable for therapeutic applications. Separately, we are working on new and improved antagonists of the P2Y14 receptor.

This technology includes MRS4322, which is an A3 agonist that is currently being evaluated for treatment of traumatic brain injury. Although its affinity in the receptor is in the micromolar range, it enters the brain in sufficient concentration to activate a protective CNS receptor, A3 adenosine receptor. Potential applications of such A3 agonists could also include neurodegenerative conditions.