Carcinogenesis inhibitor
Inventors
Mutoh, Michihiro • KUROKAWA, Yurie • Fujii, Gen • Miyamoto, Shingo
Assignees
Nippon Zoki Pharmaceutical Co Ltd • National Cancer Center Japan • National Cancer Center Korea
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Publication Number
US-11464762-B2
Publication Date
2022-10-11
Expiration Date
Abstract
A carcinogenesis inhibitor having no side effect and having an excellent effect by oral administration. A carcinogenesis inhibitor containing a hydantoin derivative or a pharmaceutically acceptable salt thereof as an active ingredient shows an inhibiting action for polyp formation and for cell proliferation, and has no side effect and highly safe whereby it is very highly useful as a pharmaceutical agent and a food such as supplement which prevent the occurrence and progress of cancer, inhibits the recurrence and metastasis of cancer and further achieves the therapeutic effect.
Core Innovation
The invention provides a hydantoin derivative represented by formula (I), where R1 is alkyl and R2 is hydrogen, and one of X and Y is hydroxyl while the other is hydrogen, hydroxy, alkyl, or alkoxy. The inhibitor includes at least one member of the hydantoin derivative formula (I) and a pharmaceutically acceptable salt, and is administered to a subject in need thereof for inhibiting carcinogenesis.
The described approach inhibits carcinogenesis by regulating expression of cell proliferation-associated factors. The document states decreased proliferation marker PCNA and decreased mRNA expression of c-Myc, CDK4, and cyclin D1 in a Min (Apc) mouse context after oral administration of a hydantoin derivative (Compound 21).
The document further states increased Gpx2 expression and altered Keap1–Nrf2 transcriptional regulation via ROS elimination in a colon cancer cell context.
Claims Coverage
The partial content identifies one independent claim and related dependent claims that refine substituents for formula (I), narrow the carcinogenesis-inhibition mechanism, and specify composition forms. Across these claims, the inventive features are the formula (I) hydantoin-derivative active ingredient with defined R1/R2 and X/Y substituent constraints, administration to a subject in need, and regulation or inhibition of proliferation-associated factor expression.
Hydantoin derivative inhibitor represented by formula (I) with defined substituents
An inhibitor comprising, as an active ingredient, at least one member of a hydantoin derivative represented by formula (I) and a pharmaceutically acceptable salt thereof, wherein R1 is alkyl and R2 is hydrogen and one of X and Y is hydroxyl and the other is hydrogen, hydroxy, alkyl or alkoxy.
Carcinogenesis inhibition method by administering the hydantoin derivative to a subject
A method for inhibiting carcinogenesis, comprising administrating the inhibitor comprising the hydantoin derivative (formula (I)) to a subject in need thereof.
Proliferation-associated factor expression regulation mechanism
Inhibiting carcinogenesis by regulating the expression of cell proliferation-associated factors.
Inhibition of c-Myc, CDK4, or cyclin D1 expression
Inhibiting carcinogenesis by inhibiting expression of c-Myc, CDK4, or cyclin D1.
The claims coverage centers on administering a formula (I) hydantoin-derivative inhibitor and pharmaceutically acceptable salt to inhibit carcinogenesis, with dependent refinements to the X/Y substituent pattern and a narrowed mechanistic scope to regulation or inhibition of proliferation-associated factor expression, specifically c-Myc, CDK4, or cyclin D1.
Stated Advantages
Low side effects, as described for oral administration.
Documented Applications
Prevention-related inhibition of carcinogenesis including occurrence and recurrence, and inhibition of metastasis, especially colorectal/colon cancer.
Use as pharmaceutical and food compositions for humans and animals, including oral preparations.
In a Min (Apc) mouse context for intestinal polyp number reduction and associated molecular changes after oral administration.
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