Methods of treating portal hypertension
AssigneeThe Charlotte-Mecklenburg Hospital Authority
InventorsTing Li, Laura Schrum, Jonel Trebicka
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Abstract
The present invention provides methods for treating or preventing portal hypertension comprising administering to a patient in need of such treatment or prevention at least one Rev-erb modulating agent (REMA) in an amount effective to treat or prevent said portal hypertension. The REMA can be SR6452 or a related compound, such as SR9009 or SR9011. The amount of the REMA administered can comprises a quantity sufficient to modulate Rev-erbα expression, activity, and/or subcellular location and/or to inhibit or reverse hepatic stellate cell (HSC) activation and contractility.
Claims17
A method of treating portal hypertension in a mammal in need thereof, the method comprising:
- detecting portal hypertension in the mammal;
- providing a composition comprising a therapeutically effective amount of one or more Rev-erb-modulating agents (REMAs), wherein the one or more REMAs is selected from the group consisting of 1,1-Dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate;
- N-Benzyl-N-(4-chlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine;
- N-Benzyl-N-(3,4-dichlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine;
- 2-((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)-N,N-dimethylacetamide;
- SR9009;
- SR9011;
- and combinations thereof, wherein the one or more REMAs is linked to a carrier/targeting moiety that selectively targets hepatic stellate cells (HSCs), and wherein the carrier/targeting moiety is mannose-6-phosphate modified human serum albumin;
- and
- administering the composition to the mammal, said therapeutically effective amount comprising a quantity sufficient to modulate at least one of Rev-erbα expression, activity, and subcellular localization in at least a portion of the mammal's HSCs for treating and/or ameliorating the portal hypertension detected in the mammal.
A pharmaceutical composition for treating portal hypertension in a mammal, the composition comprising:
- a therapeutically effective amount of one or more Rev-erb-modulating agents (REMAs), the one or more REMAs being selected from the group consisting of 1,1-Dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate, N-Benzyl-N-(4-chlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine, N-Benzyl-N-(3,4-dichlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine;
- 2-((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)-N,N-dimethylacetamide, SR9009, SR9011, and combinations thereof, and the one or more REMAs being linked to a carrier/targeting moiety that selectively targets hepatic stellate cells (HSCs),
- wherein the carrier/targeting moiety is mannose-6-phosphate modified human serum albumin;
- and
- wherein the therapeutically effective amount of the one or more REMAs is a quantity sufficient to modulate at least one of Rev-erbα expression, activity, and subcellular localization in at least a portion of the mammal's HSCs for treating and/or ameliorating portal hypertension in the mammal.
Dependencies are inferred from the claim text.