Methods and compositions for inducing ferroptosis in vivo
Inventors
Viswanathan, Vasanthi • Eaton, Jr., John Kittridge
Assignees
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Publication Number
US-11541116-B1
Publication Date
2023-01-03
Expiration Date
Abstract
Methods and systems for the induction of ferroptosis in a tissue in a subject are provided. Various ferroptosis-inducing agents a described. Various methods of administration are described for optimal ferroptosis induction and killing of target cells.
Core Innovation
The invention relates to inducing ferroptosis in vivo in a tissue of a subject. A priming agent is administered to the subject, followed by administering a ferroptosis-inducing agent in an amount sufficient to achieve a concentration of at least 1 bcM in the tissue, thereby inducing ferroptosis in vivo. The tissue is contacted with the ferroptosis-inducing agent for a period of at least 24 hours.
In one aspect, the method is used for treating cancer in a tissue of a subject by inducing ferroptosis in the tissue in vivo. The disclosure further includes a tissue concentration range of at least 1 bcM to 10 bcM. In another aspect, the ferroptosis-inducing agent achieves a distribution of 10 ng/mm^3 in the tissue for at least 4 hours.
The disclosure describes ferroptosis-inducing agents and related compositions that act through GPX4 degradation or inhibition, inhibition of glutathione related pathways including GCL and GSS, inhibition of xCT, iron chelation, lipid peroxidation, and lipoxygenase inhibition. It also describes ferroptosis-modulating agents including ferrostatin-1, liproxstatin-1, deferoxamine mesylate, methylselenocysteine, vitamin E, alpha-tocotrienol, trolox, selenium-related agents, and erythropoietin.
The disclosure further states that additional treatments may be included alongside ferroptosis modulation, such as surgery, radiation, dietary supplements, and chemotherapeutic agents, within broad pharmaceutical compositions and routes of administration. It also discusses therapeutic applications across hyperproliferative diseases including cancer, fibrosis, and autoimmune conditions.
Claims Coverage
Two independent claims are provided. The claim coverage centers on priming followed by ferroptosis induction in vivo using defined tissue exposure metrics; one claim also requires a specified tissue distribution for a minimum duration.
Priming followed by ferroptosis induction to treat cancer in vivo
Administering to the subject a priming agent, and administering to the subject a ferroptosis-inducing agent in an amount sufficient to achieve a concentration of at least 1 bcM of the ferroptosis-inducing agent in the tissue, wherein the tissue of the subject is contacted with the ferroptosis-inducing agent for a period of at least 24 hours, thereby inducing ferroptosis in the tissue in vivo and treating the cancer in the tissue of the subject.
Priming followed by ferroptosis induction with specified tissue distribution to induce ferroptosis in vivo
Administering to the subject a priming agent; and administering to the subject a composition comprising a ferroptosis-inducing agent in an amount sufficient to achieve a concentration of at least 1 bcM of the ferroptosis-inducing agent in the tissue and to achieve a distribution of 10 ng/mm^3 of the ferroptosis-inducing agent in the tissue for at least 4 hours, wherein the tissue of the subject is contacted with the ferroptosis-inducing agent for a period of at least 24 hours, thereby inducing ferroptosis in the tissue in vivo of the subject.
The claim set covers in vivo ferroptosis modulation by administering a priming agent and then a ferroptosis-inducing agent to achieve defined tissue exposure. One claim ties induction of ferroptosis to treating cancer, while the other defines additional tissue distribution requirements alongside minimum tissue concentration and at least 24 hours of tissue contact.
Stated Advantages
Treating cancer in the tissue of the subject by inducing ferroptosis in vivo.
Inducing ferroptosis in vivo in a tissue of a subject.
Documented Applications
Treating cancer in a tissue of a subject by inducing ferroptosis in the tissue in vivo.
Inducing ferroptosis in vivo in a tissue of a subject.
Therapeutic applications across hyperproliferative diseases including cancer, fibrosis, and autoimmune conditions.
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