Flip - a selective molecular target of senescent cells
AssigneeBioVentures, LLC
InventorsDaohong Zhou, Lijian Shao, Wei Feng, Jianhui Chang, Yingying Wang
Life of this patent
Estimating the term…
Abstract
The present invention relates to modulators of FLIP protein and their method of use in the treatment and prevention of diseases and pathologies related to accumulation of senescent cells during aging, such as cancer, chronic obstructive pulmonary disease (COPD), osteoarthritis, atherosclerosis, neurodegenerative diseases, diabetes, and many others. The present invention also relates to pharmaceutical compositions containing these compounds as well as various uses thereof.
Claims15
-23. (canceled)
A method of selectively killing a senescent cell, the method comprising downregulating expression of c-Fas-associated death domain-like interleukin-1 converting enzyme-like inhibitory protein (FLIP) using an agent that has an LD50 in senescent cells that is at least 3 times lower than the agent's LD50 in non-senescent cells
- wherein the senescent cell is characterized as expressing p16 and senescence-associated β-galactosidase.
A method of treating an age related condition in a subject in need thereof, comprising selectively downregulating expression of FLIP in senescent cells according to the method of claim 1, the senescent cells being contained in a tissue in the subject that is affected by the condition.
A screening method for identifying a senolytic drug that kills senescent cells with an LD50 that is at least 3 times lower than in non-senescent cells;
- the method comprising:
- (a) contacting senescent cells with a test compound;
- (b) measuring expression of c-Fas-associated death domain-like interleukin-1 converting enzyme-like inhibitory protein (FLIP) by the cells contacted with the test compound in step (a);
- (c) contacting normal (non-senescent) cells with the same test compound;
- (d) measuring expression of FLIP in the cells contacted with the test compound in step (c);
- and then
- (e) identifying the compound as a senolytic drug if the expression of FLIP is downregulated in the senescent cells but has a minimal effect on the non-senescent cells.
The method of claim 7, wherein the senescent cells and the non-senescent cells are obtained from the same cell line, the senescent cells having been treated to induce senescence.
A method of treating an age-related condition in a subject in need thereof, comprising:
- (a) identifying a senolytic drug that selectively downregulates expression of FLIP in senescent cells, thereby killing the senescent cells with an LD50 that is at least 3 times lower than the drug's LD50 in non-senescent cells;
- and
- (b) administering a pharmaceutical composition containing an amount of the senolytic drug identified instep (a) to the subject, wherein the amount of the drug in the composition and formulation of the composition are effective to alleviate a symptom of the age-related disease in the subject.
Dependencies are inferred from the claim text.