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.

Monoclonal Antibody Fragments for Targeting Therapeutics to Growth Plate Cartilage

A child's growth is dependent on the proper functioning of the growth plate, a specialized cartilage structure located at the ends of long bones and within the vertebrae. The primary function of the growth plate is to generate new cartilage, which is then converted into bone tissue and results in the lengthening of bones. Failure of the growth plate to function properly can result in short stature or sometimes a skeletal dysplasia, such as achondroplasia, in which the bones are not just short but also malformed.

Small Molecule Inhibitors of Clk and Dyrk Kinases for Potential Therapeutic Intervention of Down Syndrome, Alzheimer's Disease and Cancer

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

Glucocerebrosidase Non-inhibitory Chaperones for the Treatment of Gaucher Disease, Parkinson's Disease, and Other Proteinopathies

Gaucher disease is a rare lysosomal storage disease that is characterized by a loss of function of the glucocerebrosidase (GCase) enzyme, which results in a decreased ability to degrade its lipid substrate, glucocerebroside. The intracellular build up of this lipid causes a broad range of clinical manifestations, ranging from enlarged spleen/liver and anemia to neurodegeneration. In Gaucher disease, the loss of GCase function has been attributed to low levels of the protein in the lysosomal compartment, resulting from improper GCase folding and transport.

Heterocyclic Compounds for the Treatment of Hepatitis C Virus

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.

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.

Extended Serum Half-Life in Therapeutic Antibodies: Advancements with Enhanced lgG1 Fe Variants

This technology involves the development of lgG1 Fe variants designed to interact more effectively with the neonatal Fc receptor (FcRn) in a pH-dependent manner. By enhancing this interaction, these variants extend the serum half-life of therapeutic antibodies, reducing the need for frequent administration. This breakthrough holds the potential to make therapeutic antibody treatments more convenient, cost-effective, and accessible for a wide range of diseases.

First in class Small Molecule Agonists of the mammalian Relaxin family receptor 1 (RXFP1) and use in treatment of cancer, fibrotic, and vascular disorders (HHS Ref No. E-145-2024-0-US-02)

It is well documented in literature that activation of RXFP1 by relaxin induces: 1) up-regulation of the endothelin system which leads to vasodilation; 2) extracellular matrix remodeling through regulation of collagen deposition, cell invasiveness, proliferation, and overall tissue homeostasis; 3) a moderation of inflammation by reducing levels of inflammatory cytokines, such as TNF-a and TGF-b; and 4) angiogenesis by activating transcription of VEGF.

Subscribe to Therapeutics