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Investigators at the NIH have identified a series of novel, small molecule antagonists of the dopamine D2 receptor. Among the dopamine receptor (DAR) subtypes, D2 DAR is arguably one of the most validated drug targets in neurology and psychiatry. For instance, all receptor-based anti-Parkinsonian drugs work via stimulating the D2 DAR, whereas all FDA approved antipsychotic agents are antagonists of this receptor. Unfortunately, most agents that act as antagonists of D2 DAR are problematic, either they are less efficacious than desired or cause multiple adverse effects.

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that have changed the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Furthermore, all oral, interferon free therapeutic regimens for HCV infection will need combinations of drugs that target different aspects of the HCV life cycle.

Impaired functioning of pancreatic beta cells is a key hallmark of type 2 diabetes. Beta cell function is modulated by the actions of different classes of heterotrimeric G proteins. The functional consequences of activating specific beta cell G protein signaling pathways in vivo are not well understood at present, primarily due to the fact that beta cell G protein-coupled receptors (GPCRs) are also expressed by many other tissues.

The VRC01-class of potent, broadly neutralizing antibodies (bnAbs) targets the conserved CD4-binding site (CD4bs) of HIV-1 Env which has been a major target of HIV-vaccine design. The current best priming immunogen to engage the VRC01-class germline precursors is the eOD-GT8 60mer, which elicits VRC01-class precursors in multiple transgenic mouse models. However, a large proportion of the antibodies elicited by eOD-GT8 60mer are non-CD4bs or “off-target” antibodies, undermining its effectiveness in eliciting the VRC01-class bnAb precursors.

This technology includes the compositions and methods for inhibiting PIN1 for the treatment of disorders characterized by elevated PIN1 levels (e.g., immune disorders, proliferative disorders, and neurodegenerative disorders) with small molecules. Pin1 dysregulation has been associated with a number of pathological conditions. In particular, PIN1 has been shown to promote oncogenesis by modulating several oncogenic signaling pathways and its overexpression has been shown to correlate with poor clinical outcome.

Available for licensing through a Biological Materials License Agreement are the murine MAbs described in Beeler et al, "Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function," J Virol. 1989 Jul;63(7):2941-2950 (PubMed abs). The MAbs that are available for licensing are the following: 1129, 1153, 1142, 1200, 1214, 1237, 1112, 1269, and 1243. One of these MAbs, 1129, is the basis for a humanized murine MAb (see U.S.

Malaria continues to be a life-threatening disease, causing roughly 241 million cases and an estimated 627,000 deaths in 2020, mostly among African children, although in 2020 nearly half of the world’s population was at risk of malaria. There is a big financial burden for antimalarial treatment; direct costs (for example, illness, treatment, premature death) have been estimated to be at least US $12 billion per year and the cost in lost economic growth is many times more than that.

This technology includes compounds, pharmaceutical compositions and methods of treating or preventing neurological or psychiatric disorders for which inhibiting KCNH2-3.1 containing potassium channels provides a therapeutic effect. Polymorphisms in the KCNH2 gene have been associated with altered cognitive function and schizophrenia. The KCNH2 gene encodes the protein which forms the human ether-a-go-go related (hERG) voltage-gated potassium channel 4, 5.

This technology includes a novel chemotype against mutant (R 132H) isocitrate dehydrogenase 1 (IDH1) enzyme to be utilized as an anticancer therapy. We have progressed the structure activity relationship (SAR) and optimized the compound to be low nanomolar inhibitor of the enzyme with low nanomolar inhibition of the target in cells. These compounds lower 2-hydroxyglutarate, which has been termed an 'oncometabolite' and is common in a subset of cancers including glioma, cholangiocarcinoma, chondrosarcoma and acute myeloid leukemia.

This technology includes mutant isocitrate dehydrogenase (IDH1) inhibitors to be utilized as anticancer therapy. These potent inhibitors are aimed at lowering levels of the oncometabolite–2-hydroxyglutarate.