Patent ID: 6964853
Filing Date: 2005-11-15
Classification: A01K,A61K,A61P,C07K

Abstract:
1. A method for identifying compounds for a pharmacological agent useful in the diagnosis or treatment of disease associated with Smad6 TGF-β superfamily inhibitory activity, wherein said Smad6 (a) is encoded by the complement of nucleic acid molecules which hybridize under stringent conditions to a molecule consisting of the nucleic acid sequence of SEQ ID NO: 1 and which code for a polypeptide which inhibits TGF-β superfamily signaling, provided that the nucleic acid molecules exclude sequences consisting only of SEQ ID NO: 4, wherein the stringent conditions are selected from the group of (1) hybridization at 65° C. in hybridization buffer (3.5×SSC, 0.02% Ficoll, 0.02% polyvinyl pyrrolidone, 0.02% bovine serum albumin, 2.5 mM NaH (b) is encoded by nucleic acid molecules that differ from the nucleic acid molecules of (a) in codon sequence due to the degeneracy of the genetic code, or (c) consists of the amino acid sequence of SEQ ID NO: 2, said method comprising forming a mixture comprising a Smad6 polypeptide, a receptor or receptor complex for a TGF-β superfamily member, and a candidate pharmacological agent, incubating the mixture under conditions which, in the absence of the candidate pharmacological agent, permit a first amount of specific binding of the TGF-β superfamily receptor or receptor complex by the Smad6 potypeptide, and detecting a second test amount of the specific binding of the TGF-β superfamily receptor or receptor complex by the Smad6 polypeptide, wherein reduction of the second test amount of specific binding relative to the first amount of specific binding indicates that the candidate pharmacological agent is a compound for a pharmacological agent which disrupts the Smad6 TGF-β superfamily signal transduction inhibitory activity, and wherein increase of the test amount of specific binding relative to the first amount of specific binding indicates that the candidate pharmacological agent is a compound for a pharmacological agent which enhances the Smad6 TGF-β superfamily signal transduction inhibitory activity.