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Oxynitidine Derivatives Useful as Inhibitors of Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) for Treating Cancer

Summary: The National Cancer Institute (NCI) is actively seeking potential licensees and/or co-development research collaboration partners interested in advancing oxynitidine derivatives as novel inhibitors of topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) for cancer treatment. These TOPI and TDP1 inhibitors, when administered...

Published: 9/18/2024 | Inventor(s): Yves Pommier, Lin-kun An, Keli Agama, Evgeny Kiselev, Azhar Ravji

Keywords(s): Benzophenanthridine Derivatives, Benzophenanthridinone, Camptothecin, Dihydrobenzophenanthridine, IRINOTECAN, Oxynitidine, Pommier, Tdp1, TOP1, Topoisomerase 1B, Topotecan, Tyrosyl-DNA Phosphodiesterase 1

Category(s): Collaboration Sought > Licensing, Collaboration Sought > Collaboration, TherapeuticArea > Oncology, Application > Therapeutics

Topoisomerase III (TOP3) Inhibitors as Antiviral and Anticancer Compounds based on Bisacridines

Abstract: Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA. Thus, it is a target of interest for the development of cancer therapies and RNA viral infection therapies. TOP3B is not an essential gene for carcinogenesis, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to...

Published: 4/8/2024 | Inventor(s): Yves Pommier, Sourav Saha, Wenjie Wang, Shar-yin Huang

Keywords(s): Bisacridines, CANCER, Pommier, SARS-CoV-2, TOP, TOP3, TOP3 Inhibitor, TOPOISOMERASE, Topoisomerase III, Topoisomerase Inhibitor, viral infection

Category(s): TherapeuticArea > Infectious Disease, Collaboration Sought > Licensing, Application > Therapeutics, Collaboration Sought > Collaboration, TherapeuticArea > Oncology

Enhanced Cancer Chemotherapy Using the Bioactive Peptide Recifin And Its Analogues

Abstract: Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors...

Published: 4/8/2024 | Inventor(s): Barry O'Keefe, Lauren Krumpe, Johan Rosengren, Ingrid Schroeder, Alan Bermingham, Christophe Marchand, Kirk Gustafson, Brice Wilson, Yves Pommier

Keywords(s): CANCER, Chemosensitizing Agents, CHEMOTHERAPY, Cyclic Peptide, Irinotecan TOP1, O’Keefe, Recifin, Tdp1, Topoisomerase 1 inhibitors, Topotecan, Tyrosyl-DNA Phosphodiesterase 1 Inhibitors

Category(s): Collaboration Sought > Collaboration, TherapeuticArea > Oncology, Collaboration Sought > Licensing, Application > Therapeutics

Sensitizing Cancer Cells to DNA Targeted Therapies

Abstract: Chk2 is a protein kinase activated in response to DNA double strand breaks. In normal tissues, Chk2 phosphorylates and thereby activates substrates that induce programmed cell death, or apoptosis, via interactions with p53, E2F1, PML proteins. In cancer tissues, where apoptosis is suppressed, Chk2 phosphorylates and inactivates cell cycle...

Published: 4/8/2024 | Inventor(s): Yves Pommier, Dominic Scudiero, Christopher Self, Robert Shoemaker, David Waugh, Guangtao (George) Zhang, John Cardellina, Michael Currens, Andrew Collasanti, Charles Cook, Andrew Jobson, Sudhir Kondapaka, George Lountos

Keywords(s): Anti-cancer Therapeutic, Chk2 Inhibitors, Sensitizing Agent for current DNA-damaging cancer therapeuti

Category(s): Collaboration Sought > Licensing, TherapeuticArea > Oncology, Application > Therapeutics

Novel Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) for Treatment of Solid Tumors

Abstract: Topoisomerase 1 (TOP1) is an essential enzyme that plays a critical role in DNA transcription and replication. TOP1 inhibitors are a known class of anti-cancer agents that work to interrupt DNA replication in cancer cells, causing cell death. Since the discovery of the TOP1 inhibitor camptothecin (CPT) from plant extracts more than 60 years...

Published: 5/22/2024 | Inventor(s): Xue Zhao, George Lountos, Evgeny Kiselev, David Waugh, Yves Pommier, Terrence Burke

Keywords(s): Burke, CANCER, solid tumor, Tdp1, TOP1, Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1, Zhao

Category(s): Application > Therapeutics, Collaboration Sought > Collaboration, Collaboration Sought > Licensing, TherapeuticArea > Oncology

Synergistic Use of Exo VII Inhibitors And Quinolone Antibiotics For Treating Bacterial Infection

Abstract: Topoisomerase poisons, such as quinolone antibiotics, are widely used as anticancer drugs and antibiotics. Quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases (DNA gyrase and TOPO IV), resulting in irreversible topoisomerase cleavage complexes. However, current U.S. Food and Drug Administration (FDA) guidance reserves...

Published: 4/8/2024 | Inventor(s): Yves Pommier, Shar-yin Huang, Brianna Mitchell

Keywords(s): Antibacterial, Antibiotic Adjuvants, Antibiotic Resistance, DNA gyrase, Exonuclease VII, ExoVII, Infection, Pommier, Quinolone, TOPO IV, Topoisomerase Poisons

Category(s): Collaboration Sought > Licensing, Collaboration Sought > Collaboration, TherapeuticArea > Infectious Disease, Application > Therapeutics

Small Molecule Inhibitors of Drug Resistant Forms of HIV-1 Integrase

Abstract: Integrase strand transfer inhibitors (“INSTIs”) are currently in use as a component of prophylactic antiretroviral therapy for preventing HIV-1 infection from progressing to AIDS. Three INSTIs are approved by the FDA for inclusion in antiretroviral regiments: raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). Clinicians have already...

Published: 5/22/2024 | Inventor(s): Xue Zhao, Terrence Burke, Yves Pommier, Stephen Hughes, Mathieu Metifiot, Stephen Smith, Barry Johnson, Christophe Marchand

Keywords(s): dolutegravir, drug resistant HIV, elvitegravir, HIV therapy, Integrase, raltegravir, strand transfer

Category(s): Collaboration Sought > Collaboration, Application > Therapeutics, TherapeuticArea > Infectious Disease, Collaboration Sought > Licensing

Use of Acetalax for Treatment of Triple Negative Breast Cancer

Abstract: Triple negative (progesterone receptor (PR)-, estrogen receptor (ER)-, human epidermal growth receptor 2 (HER2)-) breast cancer (TNBC) is an aggressive subtype that affects 15-20% of the 1.7 million cases of breast cancer occurring annually. Currently, standard treatments of TNBC include cytotoxic chemotherapies, surgery, and radiation. However,...

Published: 4/8/2024 | Inventor(s): William Reinhold, Matthew Garnett, Vinodh Rajapakse, Yves Pommier, Augustin Luna

Keywords(s): Acetalax, Oxyphenisatin Acetate, Pommier, TNBC, Triple Negative Breast Cancer, Uterine Cancer

Category(s): Application > Therapeutics, Collaboration Sought > Collaboration, Collaboration Sought > Licensing, TherapeuticArea > Oncology

Novel Furoquinolinediones as Inhibitors of TDP2 and Their Potential Use to Treat Cancer

Abstract: Tyrosyl-DNA phosphodiesterase 2 (TDP2) is an enzyme that playings a critical role in repairing nucleic acid lesions, namely by repairing trapped DNA cleavage complexes. TDP2 repairs topoisomerase (TOP2)-mediated DNA damage induced by chemotherapeutic agents and removes endogenous TOP2-DNA cleavage complexes. Further, TDP2 deficiency potentiates...

Published: 4/8/2024 | Inventor(s): Christophe Marchand, Lin-kun An, Yves Pommier

Keywords(s): CANCER, Combination Therapies, Pommier, therapeutic, Topoisomerase 2 (TOP2), Tyrosyl-DNA Phosphodiesterase 2 (TDP) Inhibitors

Category(s): Collaboration Sought > Licensing, Collaboration Sought > Collaboration, TherapeuticArea > Oncology, Application > Therapeutics

Phosphodiesterase as a target for cancer therapeutics

Abstract: Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a recently discovered enzyme that catalyzes the hydrolysis of 3'-phosphotyrosyl bonds. Such linkages form in vivo following the DNA processing activity of topoisomerase I (Top1). For this reason, Tdp1 has been implicated in the repair of irreversible Top1-DNA covalent complexes, which can be generated...

Published: 9/11/2024 | Inventor(s): Yves Pommier, Periyasamy Selvam, Christophe Marchand, Thomas Dexheimer, Kasthuraiah Maddali

Keywords(s): Fluoroquinolone, PHOSPHODIESTERASE, Tdp1 inhibitors

Category(s): Collaboration Sought > Licensing, Application > Therapeutics, Collaboration Sought > Collaboration, TherapeuticArea > Oncology

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