Development of a strategy of drug development for ABC transporter-related diseases
Project/Area Number |
17H04007
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | The University of Tokyo |
Principal Investigator |
Hayashi Hisamitsu 東京大学, 大学院薬学系研究科(薬学部), 助教 (10451858)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|
Keywords | 輸送担体 / トランスポーター / 創薬 / タンパク質分解 / ABCトランスポーター |
Outline of Final Research Achievements |
To establish a strategy of drug development for ABC transporter-related diseases, we analyzed molecular mechanism underlying degradation mechanism of cell surface-resident ABCA1, an ABC transporter that has an inhibitory effect on atherosclerosis. This is based on our basic and clinical evidence obtained from studies of other ABC transporters. We have performed library screening, interactome analysis, and subsequent verification experiments using cultured cells and genetically modified mice and identified multiple molecules that promote the degradation of cell surface-resident ABCA1.
|
Academic Significance and Societal Importance of the Research Achievements |
生活習慣病から希少難病に至るまで、細胞膜に発現するABC輸送体の活性化により、治療が実現すると考えられる治療法未確立の疾患が明らかにされている。しかしながら、生体内でABC輸送体を活性化する方法論が未確立であるため、当該疾患群に対する医薬品開発は困難を極めている。本研究成果は、当該疾患群を対象とした医薬品開発の基盤構築に資する。
|
Report
(4 results)
Research Products
(16 results)
-
-
[Journal Article] Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis2019
Author(s)
Nakano S, Osaka S, Sabu Y, Minowa K, Hirai S, Kondou H, Kimura T, Azuma Y, Watanabe S, Inui A, Bessho K, Nakamura H, Kusano H, Nakazawa A, Tanikawa K, Kage M, Shimizu T, Kusuhara H, Zen Y, Suzuki M, Hayashi H.
-
Journal Title
Scientific Reports
Volume: 9
Issue: 1
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis.2018
Author(s)
Imagawa K, Hayashi H, Sabu Y, Tanikawa K, Fujishiro J, Kajikawa D, Wada H, Kudo T, Kage M, Kusuhara H, Sumazaki R.
-
Journal Title
J Hum Genet.
Volume: 印刷中
Issue: 5
Pages: 569-577
DOI
Related Report
Peer Reviewed
-
[Journal Article] Assessment of ATP8B1 Deficiency in Pediatric Patients With Cholestasis Using Peripheral Blood Monocyte-Derived Macrophages.2018
Author(s)
Hayashi H, Naoi S, Togawa T, Hirose Y, Kondou H, Hasegawa Y, Abukawa D, Sasaki M, Muroya K, Watanabe S, Nakano S, Minowa K, Inui A, Fukuda A, Kasahara M, Nagasaka H, Bessho K, Suzuki M, Kusuhara H.
-
Journal Title
EBioMedicine.
Volume: 27
Pages: 187-199
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-