Compounds that modulate processes associated with IgE production and methods and kits for identifying and using the same
AssigneeRigel Pharmaceuticals, Inc.
InventorsTodd M. Kinsella, Esteban Masuda, Mark K. Bennett, Justin E. Warner, David C. Anderson
Life of this patent
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Abstract
The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a retinoid X receptor as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.
Claims44
A method of identifying a compound that modulates IL-4 receptor-mediated IgE production or processes associated therewith, comprising determining whether the compound binds an RXR, wherein the ability to bind the RXR identifies the compound as being a modulator of IL-4 receptor-mediated IgE production or a process associated therewith.
A method of identifying compounds that modulate IL-4 receptor-mediated IgE production or processes associated therewith, comprising the step of contacting a compound from pool of candidate compounds with an RXR and identifying those compounds of the pool that bind the RXR, thereby identifying those compounds of the pool that modulate IL-4 receptor-mediated IgE production or processes associated therewith.
A compound or a pharmaceutically acceptable salt thereof having the formula (I):
- Z1—X1˜X2˜X3˜X4˜X5˜X6˜X7˜X8˜X9˜X10˜X11˜X12—Z2 (I)
- wherein:
- X1 is a small aliphatic residue or a small non-polar residue;
- X2 is a small aliphatic residue or a small polar residue;
- X3 is a Leu residue;
- X4 is a Cys residue;
- X5 is a Ser residue;
- X6is an aromatic residue;
- X7 is an aliphatic residue;
- X8is an aromatic residue;
- X9 is a polar residue;
- X10 is an aromatic residue;
- X11 is an aliphatic residue;
- X12 is an aliphatic residue;
- Z1 is RRN—, RC(O)NR—, RS(O)2NR— or an amino-terminal blocking group;
- Z2 is —C(O)OR, —C(O)O−, —C(O)NRR or a carboxyl-terminal blocking group;
- each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
- each “˜” independently represents an amide, a substituted amide or an isostere of an amide;
- each “−” represents a bond or a 1 to 10 residue peptide or peptide analog;
- and wherein one or more of X1, X2, X11, or X12 may be absent.
A method of modulating IL-4 receptor-mediated IgE production in a cell, comprising administering to the cell an effective amount of a compound that binds an RXR.
A method of inhibiting germline ε transcription in a cell, comprising administering to the cell an effective amount of a compound that binds an RXR.
A method of treating an animal suffering from a disease characterized by, caused by or associated with IgE production and/or accumulation and/or symptoms associated therewith, comprising administering to the animal an amount of a compound that binds an RXR effective to treat the disease.
A kit for identifying compounds that modulate IL-4 induced IgE production, comprising an RXR or a cell expressing an RXR and a compound that competitively binds the RXR in the presence of an active CL06 compound.
Dependencies are inferred from the claim text.