Use of Chk2 kinase inhibitors for cancer treatment
Inventors
Pommier, Yves • Shoemaker, Robert H. • Scudiero, Dominic • Currens, Michael • Cardellina, John • Jobson, Andrew
Assignees
HEALTH AND HUMAN SERVICES GOVERNMENT OF UNITED OF AMERICA, Secretary of, Department of • US Department of Health and Human Services
Publication Number
US-8912214-B2
Publication Date
2014-12-16
Expiration Date
2026-07-27
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Abstract
Described herein are Chk2-inhibitor compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
Core Innovation
The invention provides Chk2-inhibitor compounds and derivatives thereof, along with compositions and methods of treating or preventing diseases and disease symptoms using these compounds. In particular, the compounds are designed to modulate biological processes by inhibiting the Chk2 kinase, a member of the ATM-Chk2 kinase pathway, which plays a significant role in tumorigenesis and the cellular response to DNA damage.
The problem addressed is the need for effective anticancer agents that can influence the ATM-Chk2 pathway to control tumor progression. Early stages of tumorigenesis may involve DNA damage checkpoints, like the Chk2 pathway, leading to cell-cycle blockade or apoptosis. Modulating this pathway with selective Chk2 inhibitors may provide therapeutic benefit, including treatment or prevention of cancer and other diseases where apoptotic cell death is involved.
Claims Coverage
The patent claims cover three main independent inventive features related to methods of treatment and modulation involving Chk2 kinase inhibitors in subjects with specific cancers.
Method of down regulating Chk2 phosphorylation in a subject with specific cancers
This method involves identifying a subject suffering from lung cancer, breast cancer, bladder cancer, or melanoma and administering an effective amount of one or more compounds of Formulae (I) or (II) to down regulate Chk2 phosphorylation.
Method of protecting non-cancerous tissue in a subject with specific cancers
This method involves identifying a subject with lung cancer, breast cancer, bladder cancer, or melanoma and administering one or more compounds of Formulae (I) or (II) to protect non-cancerous tissue.
Method of inhibiting p53, E2F1, or PML in a normal cell in a subject with specific cancers
This method involves identifying a subject suffering from lung cancer, breast cancer, bladder cancer, or melanoma and administering an effective amount of one or more compounds of Formulae (I) or (II) to inhibit substrates p53, E2F1, or PML in normal cells.
The claims focus on therapeutic methods using compounds of Formulae (I) and (II) for treating, protecting, and modulating biological targets in subjects suffering from specific cancers, with options to include additional therapeutic agents and radiation.
Stated Advantages
Selective inhibition of Chk2 kinase over Chk1, providing specificity in treatment.
Ability to treat or prevent cancers including lung, breast, bladder, and melanoma through modulation of Chk2 phosphorylation.
Protection of non-cancerous tissue from damage during cancer treatment.
Sensitization of cancer cells to anticancer or DNA-targeted agents, potentially enhancing therapeutic efficacy.
Documented Applications
Treatment or prevention of cancers including lung cancer, breast cancer, bladder cancer, and melanoma.
Protection of non-cancerous tissue in subjects suffering from the above cancers.
Inhibition of substrates such as p53, E2F1, and PML in normal cells.
Use in combination with additional therapeutic agents, including certain anticancer agents like topotecan, irinotecan, 9-amino camptothecin, or 9-nitro camptothecin.
Administration alongside radiation therapy.
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