Use and targeting of CD98 light-chain proteins in therapies for thyroid hormone disorders
OwnerYun-Bo Shi, Peter M. Taylor +2inventors
InventorsYun-Bo Shi, Peter M. Taylor, George J. Peter, James W.A. Ritchie
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Abstract
The invention is related to the normalization of thyroid hormone transport by modulation of 4F2hc, CD98lc, and the 4F2hc-CD98lc heterodimer. Approaches to identify compounds that modulate thyroid hormone disorders, methods of identifying agonists and antagonists that modulate thyroid hormone disorders, and methods of making pharmaceuticals that ameliorate a thyroid hormone disorder are described herein.
Claims12
An isolated complex comprising a 4F2hc-CD98lc heterodimer and a thyroid hormone.
A method of ameliorating a thyroid hormone disorder comprising a step of administering a compound that modulates a 4F2hc-CD98lc heterodimer to a patient in need thereof.
A method of identifying a compound that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, or membrane vesicle or membrane fraction thereof, in a presence and absence of a test compound;
- (b) determining an amount of thyroid hormone transport mediated by said 4F2hc-CD98lc heterodimer in the presence and absence of said test compound;
- (c) selecting said test compound that alters the amount of said thyroid hormone transport;
- and
- (d) identifying said selected compound as being a candidate compound useful for the modulation of a thyroid hormone disorder.
A method of identifying a compound that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, or membrane vesicle or membrane fraction thereof, in a presence and absence of a test compound;
- (b) determining activity of said 4F2hc-CD98lc heterodimer in the presence and absence of said test compound;
- (c) selecting said test compound that alters the activity of said heterodimer;
- and
- (d) identifying said selected compound as being a candidate compound useful for the modulation of a thyroid hormone disorder.
A method of identifying a compound that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, or membrane vesicle or membrane fraction thereof, in a presence and absence of a test compound;
- (b) determining whether said test compound binds to said 4F2hc-CD98lc heterodimer;
- (c) selecting said test compound that binds to said 4F2hc-CD98lc heterodimer;
- and
- (d) identifying said selected compound as being a candidate compound useful for the modulation of a thyroid hormone disorder.
A method of identifying a compound that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, or membrane vesicle or membrane fraction thereof, in a presence and absence of a test compound;
- (b) detecting a change in expression of a 4F2hc or CD98lc gene or a change in activity of a 4F2hc or CD98lc gene product expressed by the cell;
- (c) selecting a test compound that alters said expression or activity;
- and
- (d) identifying said selected compound as being a candidate compound useful for the modulation of a thyroid hormone disorder.
A method of identifying an agonist or antagonist that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, and said heterodimer being associated with a second component that provides a detectable signal in response to binding of a compound to said heterodimer, in a presence and absence of a test compound;
- (b) determining whether said test compound binds to said 4F2hc-CD98lc heterodimer by measuring a level of a signal generated from interaction of the test compound with said heterodimer;
- (c) selecting said test compound that binds to said 4F2hc-CD98lc heterodimer;
- and
- (d) identifying said selected compound as being a candidate agonist or antagonist useful for the modulation of a thyroid hormone disorder.
The method of the above claim which further comprises conducting the identification of the agonist or antagonist in a presence of labeled or unlabeled known agonist.
A method of identifying an agonist or antagonist that can be used to modulate a thyroid hormone disorder comprising steps of:
- (a) incubating a cell that expresses a 4F2hc-CD98lc heterodimer, or membrane vesicle or membrane fraction thereof, in a presence of a known ligand, and additionally in a presence and absence of a test compound;
- (b) determining whether said test compound inhibits binding of said ligand to said 4F2hc-CD98lc heterodimer by measuring an amount of said ligand bound to said heterodimer;
- (c) selecting said test compound that causes reduction of binding of said ligand;
- and
- (d) identifying said selected compound as being a candidate agonist or antagonist useful for the modulation of a thyroid hormone disorder.
The method of the above claim in which the ligand is labeled or unlabeled known agonist.
Dependencies are inferred from the claim text.