Compositions and methods relating to inhibitors of pro-inflammatory factors for treatment of cancer
Inventors
Powell, Isaac J. • Gavande, Navnath S.
Assignees
Publication Number
US-11931360-B2
Publication Date
2024-03-19
Expiration Date
2042-06-23
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Abstract
Compositions and methods for treatment of cancer according to aspects of the present disclosure comprise compounds comprising or consisting of: structural formula (I) or (II) disclosed herein, or a salt, isomer, or derivative thereof.
Core Innovation
The invention provides compositions and methods for the treatment of cancer comprising compounds of structural formula (I) or (II), as explicitly defined in the specification. These compounds, including their salts, isomers, and derivatives (such as esters, amides, or hydrates), are formulated in pharmaceutical compositions with pharmaceutically acceptable carriers for administration to subjects in need.
The described compounds function as inhibitors of CXCR4 and at least one of the pro-inflammatory factors: TNF, IL-1beta, IL-6, and IL-8. Methods of treating a subject with cancer involve administering an effective amount of such pharmaceutical compositions, optionally alongside additional therapeutic agents (such as anti-cancer agents or inhibitors of pro-inflammatory cytokines or chemokines), as well as adjunct anti-cancer treatments including surgery and radiation.
The background discloses that, despite recent advances, there is a continuing need for new compositions and methods for the treatment of cancer. This invention addresses that need by providing new chemical entities and pharmaceutical methods to inhibit pro-inflammatory factors associated with cancer and its progression.
Claims Coverage
There are three independent claims that detail the main inventive features of the patent.
Compound with structural formula (I)
A compound comprising structural formula (I): - X is O, NH, or S - R1, R2, R3 are each independently selected from H, Br, F, methyl, Cl, OH, CN, NH2, and CF3 - R4 is H, C1-C6 unsubstituted or substituted alkyl, cycloalkyl, aryl, phenyl, heteroalkyl, heterocycloalkyl, or heteroaryl - R5 is COOH, CO2R, SO3H, SO2NH2, PO3H, CONH2, CONHOH, or SO2NHR where R is methyl, ethyl, CF3, CHF2, or CHF3 - HetAr is benzamidazolyl, benzoxazolyl, imidazopyridinyl, or imidazopyramidinyl - n1 is 0-2, n2 is 0-5, and n3 is 0-3 - The claim covers the compound and its isomer, salt, or derivative.
Pharmaceutical composition with a compound of formula (I)
A pharmaceutical composition comprising: - The compound according to claim 1 (i.e., with structural formula (I)), and - A pharmaceutically acceptable carrier.
Method of treatment of cancer with the pharmaceutical composition
A method of treatment of a subject having, or suspected of having, cancer, comprising: - Administering an effective amount of the pharmaceutical composition according to claim 5 (compound of formula (I) with a pharmaceutically acceptable carrier) to the subject.
The inventive features are directed to new compounds of structural formula (I), pharmaceutical compositions containing these compounds, and methods for treating cancer by administering such compositions.
Stated Advantages
Provides new compositions and methods for the treatment of cancer, addressing the continuing need for effective cancer therapeutics.
Enables inhibition of pro-inflammatory factors including cytokines and chemokines, and their receptors and stimulators, that are associated with cancer.
Documented Applications
Treatment of cancer in a subject by administering a pharmaceutical composition comprising the claimed compounds.
Treatment of prostate cancer, including castration resistant prostate cancer, using the disclosed compounds and compositions.
Combination therapy with additional therapeutic agents (including anti-cancer agents and inhibitors of pro-inflammatory cytokines or chemokines) and adjunct anti-cancer treatments (such as surgery and radiation).
Assaying pro-inflammatory factors such as CXCR4, TNF, IL-1beta, IL-6, and IL-8 in subject samples before and/or after treatment.
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