Screening method for SREBP pathway-specific inhibitors
AssigneesChugai Seiyaku Kabushiki Kaisha, Trustees of Dartmouth College
InventorsTa-Yuan Chang, Tatsuhiko Kodama, Takao Hamakubo, Yoshiki Kawabe
Life of this patent
Estimating the term…
Abstract
This invention provides a screening method for sterol regulatory element binding protein (SREBP) pathway-specific inhibitors using a mutant cultured cell, as well as therapeutic agents for hyperlipemia, arterial sclerosis, obesity or cancer containing an SREBP pathway-specific inhibitor selected by said screening method.
Claims7
A screening method for inhibitors specific for sterol regulatory element binding protein (SREBP) pathway, which comprises the steps of:
- a) culturing each of
- (i) mutant cells in which SCAP has lost ability to respond to sterol levels, and
- (ii) normal cells in which SCAP has not lost ability to respond to sterol levels
- in the presence and absence of a test inhibitor of SREBP pathway, and
- b) measuring both cholesterol synthesis and LDL receptor synthesis of the cells,
- wherein,
- in cells (i), if cholesterol synthesis or LDL receptor synthesis is not decreased in cells cultured in the presence of the test inhibitor compared with cells cultured in the absence of the test inhibitor,
- while in cells (ii), if both cholesterol synthesis and LDL receptor synthesis are decreased in cells cultured in the presence of the test inhibitor compared with cells cultured in the absence of the test inhibitor,
- then the test inhibitor inhibits the SREBP pathway.
A screening method for inhibitors specific for sterol regulatory element binding protein (SREBP) pathway cleavage activating protein (SCAP), which comprises the steps of:
- a) culturing each of:
- (i) mutant cells in which SCAP has lost ability to respond to sterol levels, and
- (ii) normal cells in which SCAP has not lost ability to respond to sterol levels,
- in the presence and absence of a test inhibitor of SREBP pathway, and
- b) measuring either cholesterol synthesis or LDL receptor synthesis of both of cells (i) and (ii),
- wherein,
- in cells (i), if cholesterol synthesis or LDL receptor synthesis is not decreased in cells cultured in the presence of the test inhibitor compared with cells cultured in the absence of the test inhibitor,
- while in cells (ii), cholesterol synthesis or LDL receptor synthesis is decreased in cells cultured in the presence of the test inhibitor compared with cells cultured in the absence of the test inhibitor,
- then the test inhibitor inhibits SCAP.
A screening method for inhibitors specific for Site-2 protease (S2P) in the sterol regulatory element binding protein (SREBP) pathway, which comprises the steps of:
- a) culturing each of
- (i) S2P-deficient cells and
- (ii) S2P-carrying cells,
- in the presence and absence of a test inhibitor of SREBP pathway, and
- b) measuring either cholesterol synthesis or LDL receptor synthesis of both of the cells,
- wherein,
- if cholesterol synthesis or LDL receptor synthesis is lowered in S2P-carrying cells cultured in the presence of the test inhibitor compared with S2P-carrying cells cultured in the absence of the test inhibitor,
- while cholesterol synthesis or LDL receptor synthesis is no more lowered in S2P-deficient cells cultured in the presence of the test inhibitor compared with S2P-deficient cells cultured in the absence of the test inhibitor,
- then the test inhibitor inhibits Site-2 protease (S2P) in the SREBP pathway.
Dependencies are inferred from the claim text.