IP Library Granted Patent US 9,549,908
Granted Patent B2
US 9,549,908 · App. 14/745,772 · Granted Jan 24, 2017

Composition for inducing differentiation into beige and brown adipocytes and method of inducing the same

Inventors: Kye Won Park (Suwon-si, KR); Nojoon Song (Suwon-si, KR); Suk Chan Lee (Suwon-si, KR); Jin-Mo Ku (Suwon-si, KR)
Assignees: Research & Business Foundation Sungkyunkwan University, Ltd.; Gyeonggi Institute of Science & Technology Promotion
A61K31/12A61K31/353C07D311/32C12N5/0653C12N2501/999C12N2506/1384
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Quick Facts
Patent No.
US 9,549,908
App. No.
14/745,772
Granted
Jan 24, 2017
Kind
B2
Abstract

A composition for inducing differentiation into beige adipocytes from white adipocytes, including butein, a butein derivative, or a pharmaceutically available salt thereof as an active ingredient, and a method of inducing the differentiation are provided. Increases in expressions of UCP-1 and PRDM4 are confirmed using the active ingredient, that is, the butein or butein derivative, and therefore the composition is expected to be used in preventing or treating obesity, and more basically, for target treatment.

Claims (54)

1. A composition for inducing differentiation into beige adipocytes from white adipocytes, comprising:

a compound represented by Formula 1:

where R 1 is hydrogen, halogen, linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, OH, OR S , or O(CO)R 5 , in which R 5 is linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, C2-C6 aryl, C3-C6 cycloalkyl, or C3-C10 heterocyclyl containing at least one heteroatom selected from the group consisting of N, O, and S,

where R 2 and R 3 are identical to or different from each other, each being hydrogen, halogen, linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, OH, OR 6 , or O(CO)R 6 , in which R 6 is linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, C2-C6 aryl, C3-C6 cycloalkyl, or C3-C10 heterocyclyl containing at least one heteroatom selected from the group consisting of N, O, and S,

and R 4 is hydrogen or linear or branched C1-C6 alkyl; or

a compound represented by Formula 2:

where R a , R b , and R c , are identical to or different from each other, each being hydrogen, halogen, linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, OH, OR g , or O(CO) R g , in which R g , is linear or branched C1-C6 alkenyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, C2-C6 aryl, C3-C6 cycloalky, or C3-C10 heterocyclyl containing at least one heteroatom selected from the group consisting of N, O, and S,

where R d , R e , and R f are identical to or different from each other, each being hydrogen, halogen, linear or branched C1-C6 alkyl, linear or branched C2-C6 alkyl, linear or branched C2-C6 alkynyl, OH, OR h , or O(CO)R h , in which R h is linear or branched C1-C6 alkyl, linear or branched C2-C6 alkenyl, linear or branched C2-C6 alkynyl, C2-C6 aryl, C3-C6 cycloalkyl, or C3-C10 heterocyclyl containing at least one heteroatom selected from the group consisting of N, O, and S,

or a pharmaceutically available salt thereof as an active ingredient.

2. The composition of claim 1 , wherein the compound is represented by Formula 1:

where R 1 is OH or C 1 -C 6 alkyl,

R 2 is OH, halogen or C 1 -C 6 alkoxy,

R 3 is OH or C 1 -C 6 alkoxy,

and R 4 is hydrogen or C 1 -C 6 alkyl.

3. The composition of claim 1 , wherein the compound is represented by Formula 2:

where R a , R b , and R c are identical to or different from each other, each being hydrogen or OH,

R d is OH, or C 1 -C 6 alkoxy,

R e is hydrogen, OH, halogen, or C 1 -C 6 alkoxy,

and R f is hydrogen, OH, or C 1 -C 6 alkoxy.

4. The composition of claim 1 , wherein the compound is selected from the group consisting of

2-(3,4-dihydroxyphenyl)-7-hydroxychroman-4-one;

(E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)chroman-4-one;

(E)-1-(2,4-dihydroxyphenyl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one;

7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one;

(E)-1-(2,4-dihydroxyphenyl)-3-(3-fluoro-4-hydroxyphenyl)prop-2-en-1-one;

(E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one;

2-(3,4-dihydroxyphenyl)-7-hydroxy-3-methylchroman-4-one;

2-(4-fluoro-3-methoxyphenyl)-7-hydroxychroman-4-one;

(E)-3-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one;

(E)-1,3-bis(3,4-dihydroxyphenyl)prop-2-en-1-one;

(E)-1,3-bis(4-hydroxyphenyl)prop-2-en-1-one;

(E)-1-(2-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one;

(E)-3-(2,4-dimethoxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one;

(E)-3-(2,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, and

(E)-3-(4-hydroxy-2-methoxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one.

5. The composition of claim 1 , wherein the compound increases an activity of brown adipocytes.

6. The composition of claim 1 , wherein the compound increases expression of uncoupling protein-1 (UCP-1).

7. The composition of claim 1 , wherein the compound increases expression of a PRDM4 gene.

8. A method of inducing differentiation into beige adipocytes from white adipocytes, comprising:

treating the white adipocytes with the composition of claim 1 .

9. The method of claim 8 , wherein the inducing method increases an activity of brown adipocytes.

10. A method of treating obesity, comprising:

administering the composition of claim 1 to an individual in need thereof.

11. A method of inducing differentiation into beige adipocytes from white adipocytes, comprising:

treating the white adipocytes with a composition, comprising butein, or a pharmaceutically available salt thereof, as an active ingredient.

12. The method of claim 11 , wherein the inducing method increases an activity of brown adipocytes.

13. The method of claim 11 , wherein the inducing method increases expression of uncoupling protein-1 (UCP-1).

14. The method of claim 11 , wherein the inducing method increases expression of a PRDM4 gene.

15. A method of treating obesity, comprising:

administering a composition comprising butein, or a pharmaceutically available salt thereof, as an active ingredient to an individual in need thereof.

16. The method of claim 15 , wherein the treating method increases an activity of brown adipocytes.

17. The method of claim 15 , wherein the treating method increases expression of uncoupling protein-1 (UCP-1).

18. The method of claim 15 , wherein the treating method increases expression of a PRDM4 gene.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 17, 2023
From: RESEARCH & BUSINESS FOUNDATION SUNGKYUNKWAN UNIVERSITY; GYEONGGIDO BUSINESS & SCIENCE ACCELERATOR
To: RAPPELER CO., LTD.
Reel/Frame 062392/0840 →
CHANGE OF NAME Recorded Aug 8, 2017
From: GYEONGGI INSTITUTE OF SCIENCE & TECHNOLOGY PROMOTION
To: GYEONGGIDO BUSINESS & SCIENCE ACCELERATOR
Reel/Frame 043229/0452 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2015
From: PARK, KYE WON; SONG, NOJOON; LEE, SUK CHAN; KU, JIN-MO
To: RESEARCH & BUSINESS FOUNDATION SUNGKYUNKWAN UNIVERSITY; GYEONGGI INSTITUTE OF SCIENCE & TECHNOLOGY PROMOTION
Reel/Frame 035875/0527 →
Priority Claims (2)
KR 10-2014-0078275 · Jun 25, 2014 · national
KR 10-2015-0071581 · May 22, 2015 · national
Continuity (1)
Related Publication 20150374643A1 · Dec 31, 2015