Fatty Acid Derivatives and Their Use for the Treatment and Prevention of Autoimmune, Inflammatory, and Pain Disorders

The discovery and selection of suitable compounds for the treatment and prevention of autoimmune, inflammatory, and pain disorders is a significant challenge. Researchers at National Institute of Aging (NIA) mitigated this issue. They discovered and synthesized numerous novel fatty acid derivatives (novel small molecules) that may ameliorate these conditions and provide treatment options for these disorders. In a relevant rat model, the fatty acid derivatives developed by NIA demonstrated:

Peptide Mimetic Ligands of Polo-like Kinase 1 Polo Box Domain (“Plk1 PBD Portfolio”)

Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types.  Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics.  Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.  

Peptide Mimetic Ligands of Polo-like Kinase 1 Polo Box Domain

Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types.  Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics.  Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.  

Cancer-reactive T cells from Peripheral Blood

Adoptive cell therapy (ACT) using genetically engineered T-cell receptors (TCRs) is a promising cancer treatment. These TCRs target genetic mutations unique to patients and play an important role in tumor regression. However, mutation-reactive T-cells and their TCRs can be difficult to identify and isolate from patients. Therefore, we need more efficient methods of isolating mutation-reactive T-cells for use with ACT. 

Conserved Elements Vaccine for HIV

The development of an effective HIV vaccine has been an ongoing area of research. High variability in HIV-1 virus strains, however,  represents a major challenge.  Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV.  Two major hurdles to overcome are immunodominance and sequence diversity. Researchers at the National Cancer Institute (NCI) have developed a vaccine that overcomes these major hurdles by utilizing a strategy that identifies conserved regions of the virus and exploits them for use in a targeted therapy.

MADCO-Accelerated Multidimensional Diffusion MRI

Although multidimensional diffusion/relaxation NMR experiments are widely used in materials sciences and engineering applications, preclinical and clinical MRI applications of these techniques were not feasible. Moreover, higher-field MRI scanners posed another obstacle to translation of this NMR method. Their specific absorption rate (SAR) limits the use of multi-echo or CPMG pulse trains, so that the large amounts of data required by these methods cannot be collected in vivo due to exceedingly long scan times.

Therapeutics for Neurodegenerative Disorders and Cancer Using Lenalidomide Analogs

Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-alpha), a potent activator of the immune system accompany numerous neurodegenerative diseases. TNF-alpha has been validated as a drug target with the development of the inhibitors Enbrel and Remicade (fusion antibodies) as prescription medications. Both, however, are large macromolecules that require direct injection and have limited brain access.

T Cell Receptors Targeting KRAS Mutants for Cancer Immunotherapy/Adoptive Cell Therapy

Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors. Point mutations in the KRAS gene most frequently affect amino acid position 12, resulting in the substitution of the native glycine (G) residue for other amino acids (e.g., aspartic acid (D), valine (V), cysteine (C) or arginine (R)).