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Dopamine D3 Receptor Agonist Compounds, Methods of Preparation, Intermediates Thereof, and their Methods of Use

Scientists at the National Institute on Drug Abuse (NIDA) have developed novel dopamine D3 receptor (D3R) agonists with high affinity and selectivity. Two lead compounds, 53 and eutomer 53a, have demonstrated significantly higher D3R binding selectivity than reference compounds. Moreover, 53 and 53a showed metabolic stability in liver microsomes, which is favorable for the future use of these compounds as therapeutic agents for diseases related to dopamine system dysregulation such as Parkinson’s Disease and Restless Legs Syndrome. Researchers at NIDA seek licensing and/or co-development research collaborations for the use of these D3R agonists as molecular tools for the study of D3R physiology and as potential therapeutics to treat neurological and neuropsychiatric disorders.

T-Cell Therapy Against Patient-Specific Cancer Mutations

Scientists at the National Cancer Institute's Surgery Branch developed a method to identify T cells that specifically recognize immunogenic mutations expressed only by cancer cells. The NCI seeks parties interested in collaborative research to co-develop or license T-cell therapy against cancer mutations.

Use of the TP5 Peptide for the Treatment of Cancer

Increased cyclin-dependent kinase 5 (CDK5) activity has recently emerged as a contributor to cancer progression. Researchers at the National Cancer Institute (NCI) and at the National Institute of Neurological Disorders and Stroke (NINDS) have shown that TP5, a small peptide inhibitor of CDK5 modified to facilitate passage through the blood brain barrier (BBB), has potential therapeutic benefit in glioblastoma (GBM) and colorectal carcinoma (CRC). NCI is seeking parties interested in co-developing and/or licensing TP5 for its use in the treatment of cancers with aberrant CDK5 expression as a mono-therapy or in an adjuvant setting with current standard-of-care.

Synthetic lipopeptide inhibitors of RAS oncoproteins

It is well known that overactive Ras signaling is linked to many forms of cancer, and despite intensive efforts worldwide to develop effective inhibitors of Ras, to date there is no anti-Ras inhibitor in clinical use. Researchers at the NCI’s Cancer and Inflammation Program, in collaboration with scientists at Vanderbilt University and the University of Illinois in Chicago, have identified a number of small peptidomimetic compounds that bind to Ras proteins with nanomolar affinity. NCI’s Cancer and Inflammation Program seeks partners interested in licensing or co-development of synthetic, highly potent cell-permeable inhibitors of Ras that bind to the protein directly.

Use of Acetalax for Treatment of Triple Negative Breast Cancer

The National Cancer Institute (NCI) seeks research co-development and/or potential licensees for a potential novel treatment for triple-negative breast cancer (TNBC) with acetalax (oxyphenisatin acetate). Acetalax is a previously FDA approved drug that has been used as a topical laxative but is being repurposed here as an onco-therapy because of its cytotoxic effects on a number of TNBC and other cancer cell lines.

Platform to Enhance Anti-Tumor Immunity

There is a marked increase in immunosuppressive myeloid progenitors and myeloid cells in tumors and at metastatic tissue sites, rendering these types of cells useful in cancer therapeutics, especially after genetic modifications that improve their anti-tumor properties further. The National Cancer Institute (NCI) seeks research co-development or licensing partners to further develop genetically engineered myeloid cells (GEMys) for use in cancer immunotherapy.

Angiogenesis-Based Cancer Therapeutic

The National Cancer Institute's Urologic Oncology Branch seeks interested parties to co-develop antagonists to VEGF-A and hepatocyte growth factor (HGF) that block signal transduction and associated cellular responses.

Fibroblast Growth Factor Receptor 4 (FGFR4) Monoclonal Antibodies and Methods of Their Use

Researchers at the National Cancer Institute (NCI) developed several high-affinity monoclonal antibodies to treat Fibroblast Growth Factor Receptor 4 (FGFR4)-related diseases including rhabdomyosarcoma and cancers of the liver, lung, pancreas, ovary and prostate. These antibodies have been used to generate antibody-drug conjugates (ADCs) and chimeric antigen receptors (CARs), which are capable of specifically targeting and killing diseased cells. NCI seeks co-development opportunities or licensees for this technology.

Margaric Acid Decreases PIEZO2 Mediated Pain

Investigators at the National Center for Complimentary and Integrative Health (NCCIH) and the University of Tennessee Health and Science Center have shown that administration of margaric acid can ameliorate pain induced by a variety of noxious stimuli in mice. In vitro and ex vivo studies in human and murine neural cells indicate that the mechanism of action of margaric acid is mediated by PIEZO2 (Piezo-type mechanosensitive ion channel component 2) function. NCCIH seeks research co-development partners and/or licensees for methods of using the fatty acid, margaric acid to treat pain.

Extremely Rapid Method to Isolate Neoantigen Reactive T Cell Receptors (TCRs)

Researchers at the National Cancer Institute (NCI) have developed a novel method for identifying neoantigen reactive T cells and T cell receptors (TCRs), isolated from fresh tumors of common epithelial cancers. This highly specific and sensitive method allows rapid determination of the neoantigen reactive TCR sequences and can be very useful to translate this information into TCR-engineered T-cell populations for immunotherapy without the need to grow tumor infiltrating T-cells and expensive, time-consuming screening. The NCI seeks research co-development partners and/or licensees for this invention.

Method of Neoantigen-Reactive T Cell Receptor (TCR) Isolation from Peripheral Blood of Cancer Patients

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a novel method for isolation and construction of neoantigen-reactive T-cell receptors (TCRs) from peripheral blood lymphocytes (PBL) of cancer patients. This method generates accurate scoring of single T cells from tumors, as well as facilitates identification and reconstruction of unknown TCRs for immunotherapy.

T Cell Receptors (TCRs) Specific for Mutant p53

National Cancer Institute (NCI) researchers have isolated T cell receptors (TCRs) reactive to the highly prevalent p53-R175H mutant in the context of the human leukocyte antigen (HLA) class II allele, HLA-DRB1*13:01. These TCRs can be used for a variety of therapeutic, diagnostic, and research applications. NCI seeks licensing and/or co-development research collaborations for TCRs that recognize the p53-R175H mutation and the associated HLA allele, and methods for identifying p53 mutation-reactive T cell receptors.

Combination of Near Infrared Photoimmunotherapy Targeting Cancer Cells and Host-Immune Activation

Investigators at the National Cancer Institute (NCI) seek co-development partners and/or licensees for a new therapeutic approach that selectively targets cancer cells and prevents tumor regrowth. The novel method combines antibody-IR700 molecules and Near-Infrared Photo Immunotherapy (NIR-PIT), which has shown great potential in targeting tumors via a host immunogenic response, with already known and available anti-cancer immunomodulators to further enhance the antitumor response. The investigators have shown in mouse models that, when used in combination, NIR-PIT-treatment and standard antitumor agents conferred a potent vaccine-like effect, not only curing mice of local and distant cancers but successfully immunizing them against tumor regrowth.

T-cell Receptors Targeting CD20-Positive Lymphomas and Leukemias

The National Cancer Institute (NCI) seeks licensees and/or research co-development partners for a collection of T-cell receptors (TCRs) that specifically target the CD20 antigen expressed in B-lymphoid malignancies such as non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia, and acute lymphoblastic leukemia. The TCRs are being developed as therapeutics for the treatment of lymphomas and leukemias.

Therapeutic Immunotoxins with Increased Half-Life and Anti-Tumor Activity

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for mesothelin targeting Recombinant Immunotoxins (RITs). These RITs have been engineered by site specific modification with polyethylene glycol (PEG) to have an increased serum half-life, while maintaining high cytotoxicity and have greatly improved anti-tumor activity.

High Affinity Nanobodies Targeting B7-H3 (CD276) for Treating Solid Tumors

Researchers at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 (also called B7-H3) single domain antibodies (also known as nanobodies). These antibodies have a high affinity for CD276-positive tumor cells and have great potential for diagnostic and therapeutic technologies against solid tumors. The NCI seeks licensing and/or co-development research collaborations for CD276-targeting camel nanobodies.

Compounds that Interfere with the Androgen Receptor Complex

NCI researchers have identified novel compounds that inhibit FKBP52-mediated activation of the androgen receptor protein (AR), a major target for anti-prostate cancer therapeutic development. As FKBP52 is implicated in the regulation of other hormone receptors, anti-FKBP52 may be applicable in the treatment of hormone-dependent diseases such as diabetes or even used as contraceptives. NCI seeks partners to license or co-develop this technology.

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