CD206 Small Molecule Modulators, Their Use and Methods for Preparation

Pancreatic ductal adenocarcinoma (PDA) accounts for more than 90% of pancreatic cancer cases, and it is one of the most aggressive malignancies with a 5-year survival rate of 6%. The high mortality rate caused by PDA is primarily from the lack of early diagnosis – it is often asymptomatic in early stages – and a poor response to conventional chemotherapy and radiotherapy. One of the major immune cell types present in the PDA microenvironment is a subset of macrophages commonly termed tumor-associated macrophages (TAM).

Autophagy Modulators For Use in Treating Cancer

Cancer cells can upregulate autophagy – cell destruction – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that compounds identified by screening a library of compounds blocks autophagy in some cancer cells (e.g., melanoma) but are not toxic to normal cells. Cancer cells with mutations in the BRAF oncogene are especially dependent on autophagy. Treatment of cancer cells with the BRAF mutation can increase the efficacy of chemotherapy.

Drug Repurposing to Treat Merkel Cell Carcinoma (MCC)

Merkel Cell Carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin.  It is most commonly found on areas of the skin with higher ultraviolet (UV) exposure, and in Caucasian patients of advanced age.  Interestingly, approximately 80% of MCC tumors are caused by integration of the Merkel cell polyomavirus (MCPyV) into the host genome (VP-MCC).  The remaining 20% are virus negative (VN-MCC) and caused by somatic mutations induced by UV exposure.  

Niclosamide for Treating Adrenocortical Cancer (ACC)

ACC is a rare but lethal malignancy. There is currently a lack of effective therapies for advanced and metastatic ACC patients. In fact, most patients develop a recurrence even after complete surgical resection. The emerging field of drug repositioning provides new possibilities for ACC treatment with advantages such as existing pharmacological and toxicity data to help accelerate therapy development. For rare cancers, such as ACC, drug repositioning can play an essential role in finding a treatment for a disease that may otherwise be neglected due to high costs. 

Cancer Therapeutic Based on Hypoxia Inducible Factor 1 (HIF-1) Inhibitors

Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.

BODIPY-FL Nilotinib (Tasigna) for Use in Cancer Research

The National Cancer Institute''s Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize bodipy conjugated tyrosine kinase inhibitors that are currently used in the clinic for the treatment of CML or gastric cancers. We are also interested in evaluating third generation tyrosine kinase inhibitor derivatives as modulators of ABC drug transporters to improve the efficiency of chemotherapy in animal (mouse) model system.

Functional Brain Region-Specific Neural Spheroids for Modeling Neurological Diseases and Therapeutics Screening

3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. The present invention presents a method for generating functional neural spheroids with differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.

Identification of a novel and selective D3 dopamine receptor-selective agonist

This technology relates to the description and therapeutic use of a small molecule that selectively binds to and activates the D3 dopamine receptor. Dopamine receptors (DARs) are members of the G protein-coupled receptor (GPCR) superfamily that play a critical role in cell signaling processes, especially modulating the transfer of information within the nervous system. Members of the DAR subfamilies share high sequence homology, especially the D2 and D3 DARs. Most currently available dopaminergic drugs cross-react with both subtypes to varying degrees.

Synthesis and Use of Positive Allosteric Modulators to Modify D1 Dopamine Receptor Activity

This technology relates to the creation and use of newly identified ligands to the D1 dopamine receptor (D1R). The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. These ligands are positive allosteric modulators (PAMs) that bind to the dopamine receptor at a site other than where dopamine binds and causes the receptor to have an increased response.

First-in-class Small Molecule Agonists of the Insulin-like (INSL3) Peptide Receptor RXFP2 and Uses in Bone Disorders and Fertility

Recent studies have identified the G-protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of bone diseases such as osteoporosis and rare bone diseases such as osteogenesis imperfecta. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. A stable, orally deliverable drug is a much more desirable alternative. Our RXFP2 agonists perform as well as the natural ligand INSL3 in cellular assays.