KILLING SENESCENT CELLS AND TREATING SENESCENCE-ASSOCIATED CONDITIONS USING A SRC INHIBITOR AND A FLAVONOID
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
A61K-031/506
A61K-031/352
출원번호
US-0113723
(2015-01-28)
공개번호
US-0216286
(2017-08-03)
국제출원번호
PCT/US15/13376
(2015-01-28)
발명자
/ 주소
Kirkland, James L.
Tchkonia, Tamar
Zhu, Yi
Palmer, Allyson K.
LeBrasseur, Nathan K.
Miller, Jordan D.
출원인 / 주소
Kirkland, James L.
인용정보
피인용 횟수 :
0인용 특허 :
0
초록▼
Provided herein are methods and uses for treatment or prophylaxis of a senescent cell associated disease or disorder by administering a senolytic combination comprising dasatinib and quercetin or an analog thereof to a subject in need thereof. In certain embodiments, the senescent cell associated di
Provided herein are methods and uses for treatment or prophylaxis of a senescent cell associated disease or disorder by administering a senolytic combination comprising dasatinib and quercetin or an analog thereof to a subject in need thereof. In certain embodiments, the senescent cell associated disease or disorder is a cardiovascular disease or disorder, inflammatory disease or disorder, a pulmonary disease or disorder, a neurological disease or disorder, or a metabolic disease or disorder.
대표청구항▼
1. A method for treating a senescence associated disease or disorder in a subject comprising administering to the subject a senolytic combination, wherein the senescence associated disease or disorder is not cancer; andwherein the senolytic combination includes a src inhibitor and a flavonoid. 2. Th
1. A method for treating a senescence associated disease or disorder in a subject comprising administering to the subject a senolytic combination, wherein the senescence associated disease or disorder is not cancer; andwherein the senolytic combination includes a src inhibitor and a flavonoid. 2. The method of claim 1, wherein the senolytic combination is administered once every 0.5-12 months; provided that if the senescence associated disease or disorder is a senescence associated metabolic disorder, the senolytic combination is administered once every 4-12 months. 3. (canceled) 4. The method of claim 1, wherein the senescence associated disease or disorder is atherosclerosis. 5. The method of claim 1, wherein the senescence associated disease or disorder is osteoarthritis. 6. The method of claim 1, wherein the senescence associated disease or disorder is idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease. 7. (canceled) 8. The method of claim 1, wherein the senescence associated disease or disorder is selected from diabetes, metabolic syndrome, and obesity. 9.-10. (canceled) 11. A method of killing a senescent cell, comprising contacting the senescent cell with a src inhibitor and a flavonoid. 12. The method of claim 11, wherein the senescent cell is selected from a senescent fibroblast, a senescent pre-adipocyte, a senescent epithelial cell, a senescent chondrocyte, a senescent neuron, and a senescent endothelial cell. 13. The method of claim 11, wherein the senescent cell is a senescent pre-adipocyte. 14. The method of claim 11, wherein the src inhibitor is dasatinib. 15. The method of claim 11, wherein the flavonoid is a compound having a structure of the following formula (I): or a pharmaceutically acceptable salt thereof, wherein R1 is —OH or —H;R2 is —OH or —H;R3 is —OH, —H, —R6, or —OCH2PO(OH)2;R4 is —OH, —OPO(OH)2, —OCH3, —OCH2PO(OH)2, —R6, —H, or —OSO3H; andR5 is —OH, —H, —R6, or —OCH3,wherein R6 is 16. (canceled) 17. The method of claim 15 wherein R3 is —OH. 18.-19. (canceled) 20. The method of claim 15 wherein R4 is —OH or —OSO3H. 21. The method of claim 15 wherein R5 is —OH. 22. The method of claim 15 wherein the compound of Formula (I) is selected from the following structures and pharmaceutically acceptable salts thereof: 23. The method of claim 1, wherein the senolytic combination is administered during a treatment course of 1-7 days once every 0.5-12 months. 24. The method of claim 1, wherein the senescence associated disease or disorder is a senescence associated metabolic disorder, and the senolytic combination is administered during a treatment course of 1-7 days once every 4-12 months. 25. The method of claim 1, wherein the src inhibitor is dasatinib. 26. The method of claim 1, wherein the flavonoid is a compound having a structure of the following formula (I): or a pharmaceutically acceptable salt thereof, wherein R1 is —OH or —H;R2 is —OH or —H;R3 is —OH, —H, —R6, or —OCH2PO(OH)2;R4 is —OH, —OPO(OH)2, —OCH3, —OCH2PO(OH)2, —R6, —H, or —OSO3H; andR5 is —OH, —H, —R6, or —OCH3; wherein R6 is 27. The method of claim 26, wherein the compound of Formula (I) is selected from the following structures and pharmaceutically acceptable salts thereof:
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