Patents
Track Code 2021-CHOP-69413
Brief summary
Researchers at Purdue University have developed new pH-activable fluorescent probes for targeting cell organelles in live cells. Unlike traditional multi-step probes for live-cell organelle imaging, this technology requires the use of a common intermediate probe only. In addition, currently, only a few sensing and imaging technologies are commercially available that are responsive to pH; and activation or deactivation by pH can be used to improve targeting to specific cells and organelles. The robust probes created by Purdue researchers emit high fluorescence at the acidic pH of the organelle and negligible fluorescence at cytosolic neutral pH. The probes are soluble, cell-permeable, and readily taken up by target organelles. This platform uses a single molecular scaffold that can be implemented in a variety of applications in drug discovery and other investigations of cellular biology. The researchers have designed three probes using this platform that localize to the lysosome, mitochondria, or nucleus, respectively, and are activated upon uptake by the organelles. These probes were tested in live BV2 microglial cells and had little effect on cellular metabolism. Using primary microglial cells and BV2 cells, the cellular localization was confirmed with confocal microscopy, and the technology was demonstrated to be compatible with cell sorting by flow cytometry.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu
Track Code 2020-CHOP-68949
Brief summary
Purdue University researchers have developed a potent small molecule for use in cancer immunotherapy which acts by inhibiting the Programmable Cell Death Protein 1/Programmable Death-Ligand 1 (PD-1/PD-L1) interaction. Cancer cells express PD-L1, a cell surface protein that binds to PD-1 on T-cells, debilitating anti-cancer immunity. Antibodies targeting the PD-1/PD-L1 interaction have proven to be a viable therapeutic strategy toward mitigating cancer growth but suffer from high production costs, limited administration techniques, and low therapeutic indices. To address these limitations, Purdue University researchers created a small molecule inhibitor of the PD-1/PD-L1 interaction that specifically target PD-1 dimerization. The researchers developed the new molecule through robust computational modeling of publicly available PD-1/PD-L1 inhibitory data. In homogenous time-resolved fluorescence binding assays the Purdue compound exhibited about 1.6 fold increased potency in inhibiting the PD-1/PD-L1 interaction compared to a positive control molecule known from the patent literature (IC50 = 339.9 nM and 521.5 nM, respectively). Further medicinal chemistry optimization promises to increase potency and yield an excellent preclinical candidate for use in small molecule immune checkpoint blockade therapy.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu
Track Code 2019-CHOP-68541
Brief summary
Researchers at Purdue University have developed pH-dependent fluorogenic amyloid-beta reporters for the study of Alzheimer's disease (AD). Microglial phagocytosis of amyloid-beta peptides is a critical step in the regulation of brain homeostasis during the initiation and progression of AD. Unlike common methods to study this phenomenon, this technology is specific for amyloid-beta and functions in live cells. The reporter, an isoform of human amyloid-beta tagged with a pH-dependent fluorogenic moiety, fluoresces only upon phagocytosis in the acidic intracellular phagosomes. It clearly differentiates between phagocytic and non-phagocytic cells within live human and nonhuman microglial cells. This technology promises to aid in the discovery of new therapeutics for AD.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu
Track Code 2019-CHOP-68541
Brief summary
Researchers at Purdue University have developed pH-dependent fluorogenic amyloid-beta reporters for the study of Alzheimer's disease (AD). Microglial phagocytosis of amyloid-beta peptides is a critical step in the regulation of brain homeostasis during the initiation and progression of AD. Unlike common methods to study this phenomenon, this technology is specific for amyloid-beta and functions in live cells. The reporter, an isoform of human amyloid-beta tagged with a pH-dependent fluorogenic moiety, fluoresces only upon phagocytosis in the acidic intracellular phagosomes. It clearly differentiates between phagocytic and non-phagocytic cells within live human and nonhuman microglial cells. This technology promises to aid in the discovery of new therapeutics for AD.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu
Track Code 2019-CHOP-68534
Brief summary
Researchers at Purdue University have developed potent synthetic small molecules with high potential as drugs against castration-resistant prostate cancer (CRPC) that are non-toxic in normal human cell lines. To address the heterogeneity of cellular pathways in cancer, the source of a cancer's ability to become resistant to therapy, the investigators designed these molecules using a machine learning approach that targets the protein network implicated in the disease state to guide compound selection and synthesis. The series of compounds developed inhibits proliferation of C4-2 androgen-insensitive human prostate adenocarcinoma cells with IC50 as low as 0.72 nM, and the compounds are much more potent than a control, the current steroidal CRPC drug, abiraterone (ABI). The most potent compound and other active leads were also more metabolically stable than ABI in a mouse liver microsome assay. Further, these compounds promise to combat metastasis; they slow migration of cells relative to untreated cells in both LNCaP and C4-2 cell lines.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu
Track Code : 2018-CHOP-68209
Brief summary
Surface modification of live cells has many biomedical and therapeutic applications, such as live cell imaging and cell therapy. The current approaches have limitations including poor stability over time and incompatibility with mammalian cells due to toxicity. There is a need for a new technology that improves surface modification of live cells. Researchers at Purdue University have developed a new technology that enables surface modification of live mammalian cells. This cell-modification technology has applications in live cell imaging, manufacturing of cell therapies, enhancement of cells for therapeutic applications, cell-drug conjugation for enhanced killing of cancer cells, and drug delivery in a pH dependent manner to sites of inflammation. This technology conjugates small molecules, proteins, fluorophores, and PET tracers to live cells without nanoparticles or other vehicles.
Contact information: OTC: otcip@prf.org ; gchopra@purdue.edu