New drug development targeting novel renal tubular rate transporter MCT9 based on the structure-activity relationship
| Project/Area Number |
18K08200
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53040:Nephrology-related
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
ANZAI Naohiko 千葉大学, 大学院医学研究院, 教授 (70276054)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
大内 基司 獨協医科大学, 医学部, 准教授 (20409155)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | トランスポーター / 痛風 / 高尿酸血症 / 創薬 |
|---|
| Outline of Final Research Achievements |
In this study, we analyzed two points: (A) synthesis of inhibitory compounds based on the elucidation of the structure-activity relationship of uric acid transport by the novel uric acid transporter MCT9, and (B) identification of MCT9-binding protein and details of transport control mechanism. In (A), we succeeded in constructing an expression plasmid having a full-length MCT9 sequence and producing MCT9-expressing HEK293 cells. We performed compound screening using the Chiba Chemical Library. In (B), as a result of screening the kidney cDNA library from the preparation of a bait vector having the intracellular C-terminal sequence of MCT9 and the confirmation of protein expression in yeast cells, we obtained a positive clone that seems to be a candidate for MCT9-binding protein.
|
| Academic Significance and Societal Importance of the Research Achievements |
我が国では痛風患者は100万人を越えるとされ、痛風発症の基盤となる高尿酸血症患者に至っては1,000万人いると推定されている。痛風発症機序は未だに明らかにされておらず、その発症予防には血清尿酸値を低く保つことが必要である。そのため副作用の少ない新規の尿酸降下薬開発は今後も必須の課題である。本研究で新規尿酸トランスポーターMCT9の結合タンパク質候補の同定に迫ったことは新たな治療標的の解明につながることが期待される。また今回明確なMCT9阻害候補化合物の同定に至らなかったものの、阻害しないという構造情報も新規化合物合成に活用可能であり、創薬の基盤情報として貢献できる。
|
Report
(4 results)
Research Products
(23 results)
-
-
-
-
-
-
-
-
[Journal Article] Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin.2018
Author(s)
Fu Y, Breljak D, Onishi A, Batz F, Patel R, Huang W, Song P, Freeman B, Mayoux E, Koepsell H, Anzai N, Nigam SK, Sabolic I, Vallon V.
-
Journal Title
Am J Physiol Renal Physiol.
Volume: 315
Issue: 2
Pages: F386-F394
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models.2018
Author(s)
Hori T, Ouchi M, Otani N, Nohara M, Morita A, Otsuka Y, Jutabha P, Shibasaki I, Matsushita Y, Fujita T, Fukuda H, Anzai N.
-
Journal Title
J Pharmacol Sci
Volume: 136
Issue: 4
Pages: 196-202
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Synthesis of novel benzbromarone derivatives designed to avoid metabolic activation.2018
Author(s)
Ohe T, Umezawa R, Kitagawara Y, Yasuda D, Takahashi K, Nakamura S, Abe A, Sekine S, Ito K, Okunushi K, Morio H, Furihata T, Anzai N, Mashino T.
-
Journal Title
Bioorg Med Chem Lett
Volume: 28
Issue: 23-24
Pages: 3708-3711
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
[Book] エース薬理学2020
Author(s)
金井好克、安西尚彦、安藤 仁、浅井 聰
Total Pages
303
Publisher
南山堂
ISBN
9784525140717
Related Report
