Patents by Inventor Paul J. Hergenrother
Paul J. Hergenrother has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20220112203Abstract: Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.Type: ApplicationFiled: May 3, 2021Publication date: April 14, 2022Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Michelle Richter, Andrew Riley, Bryon S. Drown, Martin Chavez, Sarah Tasker, Alfredo Garcia
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Publication number: 20220089602Abstract: The diterpene natural product pleuromutilin was subjected to reaction sequences focused on creating ring system diversity in few synthetic steps. This effort resulted in a collection of compounds with previously unreported ring systems, providing a novel set of structurally diverse and highly complex compounds suitable for screening in a variety of different settings. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide is an inhibitor of thioredoxin, a key component of the antioxidant system in the cell. Ferroptocide positively modulates the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.Type: ApplicationFiled: October 5, 2021Publication date: March 24, 2022Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Evijola Llabani
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Publication number: 20220088019Abstract: Compositions and methods for the induction of cancer cell death. The compositions and methods include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds and can be effective when a particular cancer has become resistant to previously administered therapies.Type: ApplicationFiled: September 28, 2021Publication date: March 24, 2022Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. HERGENROTHER, Jessie PEH
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Patent number: 11274106Abstract: Herein is described the conversion of deoxynybomycin (DNM), a natural product and DNA gyrase inhibitor with minimal cytotoxicity, into a compound (Formula I) that has anticancer activity. Detailed in vitro and cell culture experiments demonstrate that these compounds inhibit Top2 and also act upon topoisomerase I. Similar approaches are applicable to other classes of gyrase inhibitors and other antibacterial targets for discovery of new anticancer drugs.Type: GrantFiled: June 21, 2018Date of Patent: March 15, 2022Assignee: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Andrew P. Riley
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Publication number: 20220050112Abstract: The post-translational modification (PTM) and signaling molecule poly(ADP-ribose) (PAR) has an impact on diverse biological processes. PTM is regulated by a series of ADP-ribosyl glycohydrolases (PARG enzymes) that cleave polymers and/or liberate monomers from their protein targets. Disclosed herein is a substrate for monitoring PARG activity, TFMU-ADPr, which directly reports on total PAR hydrolase activity via release of a fluorophore; this substrate has excellent reactivity, generality, stability, and usability. A second substrate, TFMU-IDPr, selectively reports on PARG activity only from the enzyme ARH3. Use of these probes in whole-cell lysate experiments has revealed a mechanism by which ARH3 is inhibited by cholera toxin. TFMU-ADPr and TFMU-IDPr are versatile tools for assessing small-molecule inhibitors in vitro and probing the regulation of ADP-ribosyl catabolic enzymes.Type: ApplicationFiled: September 9, 2019Publication date: February 17, 2022Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Bryon S. DROWN
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Publication number: 20220000862Abstract: Synergistic drug combinations with the small molecule PAC-1 against uveal or cutaneous melanoma. There are no current targeted drug treatments for the mutations associated with uveal melanoma. Despite primary radiation or surgical therapy, up to 50% of patients eventually develop metastatic disease, for which there is no standard therapy nor treatment shown to improve overall survival. Drug combinations with PAC-1 allow the use of lower dosages of this compound that result in cancer cell death in uveal melanoma. Drug combinations of PAC-1 with the kinase inhibitor entrectinib have shown a synergistic effect against uveal melanoma cell lines. Specifically, PAC-1 and entrectinib are synergistic against wild-type and mutant uveal melanoma cell lines (e.g., GNAQ and GNA11).Type: ApplicationFiled: October 3, 2019Publication date: January 6, 2022Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. HERGENROTHER, Matthew Wesley BOUDREAU
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Publication number: 20210395839Abstract: A saliva-based testing method that bypasses the need for RNA isolation/purification is described herein. In experiments with inactivated SARS-CoV-2 virus spiked into saliva, this method has a limit of detection of 500-1000 viral particles per mL, rivalling the standard NP swab method. Initial studies showed excellent performance with 100 clinical samples. This saliva-based process is operationally simple, utilizes readily available materials, and can be easily implemented by existing testing sites thus allowing for high-throughput, rapid, and repeat testing of large populations.Type: ApplicationFiled: June 17, 2021Publication date: December 23, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: Diana Rose RANOA, Robin L. HOLLAND, Fadi G. ALNAJI, Kelsie J. GREEN, Leyi WANG, Christopher B. BROOKE, Martin D. BURKE, Timothy M. FAN, Paul J. HERGENROTHER
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Publication number: 20210340100Abstract: A set of small molecules ER? biomodulators that kill therapy-resistant ER? positive breast, ovarian, and endometrial cancer cells. These small molecules have increased therapeutic potential because of an increased ability to kill therapy-resistant breast cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/ICI). The new compounds do not only inhibit proliferation of the cancer cells but actually kills them, which prevents reactivation of tumors years later.Type: ApplicationFiled: May 13, 2021Publication date: November 4, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: David J. SHAPIRO, Paul J. HERGENROTHER, Matthew W. BOUDREAU
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Publication number: 20210315886Abstract: New synthetic methods to provide access to previously unexplored functionality at the C8 position of imidazotetrazines. Through synthesis and evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5 to 40 hours), a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent was derived. Promising compounds were identified that possess activity against a panel of GBM cell lines, appropriate hydrolytic and metabolic stability, and brain-to-serum ratios dramatically elevated relative to TMZ, leading to lower hematological toxicity profiles and superior activity to TMZ in a mouse model of GBM.Type: ApplicationFiled: August 9, 2019Publication date: October 14, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. HERGENROTHER, Timothy M. FAN, Riley L. SVEC
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Patent number: 11129830Abstract: Compositions and methods for the induction of cancer cell death. The compositions and methods of using them include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds and can be effective when a particular cancer has become resistant to previously administered therapies.Type: GrantFiled: June 10, 2019Date of Patent: September 28, 2021Assignee: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Jessie Peh
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Publication number: 20210290616Abstract: The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.Type: ApplicationFiled: December 22, 2020Publication date: September 23, 2021Applicants: The Board of Trustees of the University of Illinois, Vanquish Oncology, Inc., The Johns Hopkins UniversityInventors: Paul J. Hergenrother, Rachel C. BOTHAM, Timothy M. FAN, Mark J. GILBERT, Michael K. HANDLEY, Avadhut JOSHI, Gregory J. RIGGINS, Theodore M. TARASOW
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Publication number: 20210276951Abstract: A set of small molecules ER? biomodulators that kill therapy-resistant ER? positive breast, ovarian, and endometrial cancer cells. These small molecules have increased therapeutic potential because of an increased ability to kill therapy-resistant breast cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/ICI). The new compounds do not only inhibit proliferation of the cancer cells but actually kills them, which prevents reactivation of tumors years later.Type: ApplicationFiled: July 1, 2019Publication date: September 9, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: David J. SHAPIRO, Paul J. HERGENROTHER, Matthew W. BOUDREAU
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Patent number: 11046647Abstract: A set of small molecules ER? biomodulators that kill therapy-resistant ER? positive breast, ovarian, and endometrial cancer cells. These small molecules have increased therapeutic potential because of an increased ability to kill therapy-resistant breast cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/ICI). The new compounds do not only inhibit proliferation of the cancer cells but actually kills them, which prevents reactivation of tumors years later.Type: GrantFiled: February 26, 2020Date of Patent: June 29, 2021Assignee: The Board of Trustees of the University of IllinoisInventors: David J. Shapiro, Paul J. Hergenrother, Matthew W. Boudreau
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Publication number: 20210128551Abstract: The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.Type: ApplicationFiled: January 8, 2021Publication date: May 6, 2021Applicants: The Board of Trustees of the University of Illinois, Vanquish Oncology, Inc.Inventors: Paul J. HERGENROTHER, Rachel C. BOTHAM, Timothy M. FAN, Mark J. GILBERT, Michael K. HANDLEY, Howard S. ROTH, Theodore M. TARASOW
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Patent number: 10995097Abstract: Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.Type: GrantFiled: March 13, 2017Date of Patent: May 4, 2021Assignee: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Michelle Richter, Andrew Riley, Bryon Drown, Martin Chavez, Sarah Tasker, Alfredo Garcia
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Publication number: 20210017165Abstract: Disclosed herein are antibacterial compounds that accumulate in Gram-negative bacteria, methods of preparing the compounds, and methods of using the compounds to inhibit or kill microbes, and methods of treating microbial infections, such as Gram-negative bacterial infections. Compounds selected for conversion to potential Gram-negative antibacterial compounds were identified based on compounds having low globularity and low flexibility. Amine substituents were then strategically added to the selected compounds to provide compounds having antibacterial activity against Gram-negative bacteria.Type: ApplicationFiled: March 11, 2019Publication date: January 21, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. HERGENROTHER, Emily Jane GEDDES, Bryon Shane DROWN, Stephen E. MOTIKA, Erica Nicole PARKER
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Patent number: 10888560Abstract: The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.Type: GrantFiled: October 1, 2018Date of Patent: January 12, 2021Assignees: The Board of Trustees of the University of Illinois, Vanquish Oncology, Inc.Inventors: Paul J. Hergenrother, Rachel C. Botham, Timothy M. Fan, Mark J. Gilbert, Michael K. Handley, Howard S. Roth, Theodore M. Tarasow
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Publication number: 20210002286Abstract: New synthetic methods to provide access to previously unexplored functionality at the C8 position of imidazotetrazines. Through synthesis and evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5 to 40 hours), a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent was derived. Promising compounds were identified that possess activity against a panel of GBM cell lines, appropriate hydrolytic and metabolic stability, and brain-to-serum ratios dramatically elevated relative to TMZ, leading to lower hematological toxicity profiles and superior activity to TMZ in a mouse model of GBM.Type: ApplicationFiled: September 10, 2020Publication date: January 7, 2021Applicant: The Board of Trustees of the University of IllinoisInventors: Paul J. HERGENROTHER, Timothy M. Fan, Riley L. Svec
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Patent number: 10874666Abstract: The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.Type: GrantFiled: October 1, 2018Date of Patent: December 29, 2020Assignees: The Board of Trustees of the University of Illinois, Vanquish Oncology, Inc., The Johns Hopkins UniversityInventors: Paul J. Hergenrother, Rachel C. Botham, Timothy M. Fan, Mark J. Gilbert, Michael K. Handley, Avadhut Joshi, Gregory J. Riggins, Theodore M. Tarasow
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Patent number: 10800730Abstract: The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.Type: GrantFiled: September 20, 2018Date of Patent: October 13, 2020Assignee: The Board of Trustees of the University of IllinoisInventors: Paul J. Hergenrother, Robert W. Huigens, III, Karen C. Morrison, Robert W. Hicklin, II, Timothy A. Flood, Jr.