Inhibitors of receptor activator of NF-kappaB and uses thereof
OwnerBharat B. Aggarwal, Bryant G. Darnay +1inventors
InventorsBharat B. Aggarwal, Bryant G. Darnay, Sujay Singh
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Abstract
The present invention provides a RANK (receptor activator of NF-κB) inhibitor consisted of a TRAF-6 (TNF receptor-associated factor-6) binding domain attached to a leader sequence. The decoy peptide inhibits RANKL (RANK ligand)-mediated osteoclast differentiation, thus indicating that targeted disruption of interaction between RANK and TRAF6 may prove useful as a therapeutic for metabolic bone disorders, leukemia, arthritis, and metastatic cancer of the bone.
Claims35
A polypeptide that inhibits signaling mediated by TNF receptor-associated factor 6 (TRAF6), wherein said polypeptide comprises a TRAF6 binding domain and a leader signal sequence.
A method of identifying a non-peptide small molecule capable of inhibiting interaction between receptor activator of NF-κB (RANK) and TNF receptor-associated factor 6 (TRAF6), comprising the step of:
- preparing a polypeptide comprising a TRAF6 binding domain;
- and
- examining binding of TRAF6 to said polypeptide in the presence and absence of a non-peptide small molecule, wherein reduced binding in the presence of said non-peptide small molecule would indicate that said non-peptide small molecule is capable of inhibiting RANK-TRAF6 interaction.
A non-peptide analog that mimics the function of a polypeptide comprising a TNF receptor-associated factor 6 (TRAF6) binding domain and a leader signal sequence, wherein said polypeptide inhibits signaling mediated by TRAF6.
Dependencies are inferred from the claim text.