Method for identifying compounds that affect Smad7 binding
AssigneeLudwig Institute for Cancer Research
InventorsAtsuhito Nakao, Carl-Henrik Heldin, Peter ten Dijke
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Abstract
The invention describes nucleic acids encoding the Smad7 protein, including fragments and biologically functional variants thereof. Also included are polypeptides and fragments thereof encoded by such nucleic acids, and antibodies relating thereto. Methods and products for using such nucleic acids and polypeptides also are provided.
Claims7
A method for identifying a lead compound for a pharmacological agent useful in the diagnosis or treatment of disease associated with Smad7 TGF-β superfamily inhibitory activity, comprising
- forming a mixture comprising a Smad7 polypeptide, a TGF-β superfamily receptor complex, 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 complex by the Smad7 polypeptide, and
- detecting a test amount of the specific binding of the TGF-β superfamily receptor complex by the Smad7 polypeptide, wherein reduction of the test amount of specific binding relative to the first amount of specific binding indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which disrupts the Smad7 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 lead compound for a pharmacological agent which enhances the Smad7 TGF-β superfamily signal transduction inhibitory activity.
A method for identifying a lead compound for a pharmacological agent useful in the diagnosis or treatment of disease associated with Smad7 TGF-β superfamily signal transduction inhibitory activity, comprising
- forming a mixture comprising a Smad7 polypeptide, a TGF-β superfamily receptor complex or an activated TGF-β superfamily type I receptor, a pathway specific Smad polypeptide and a candidate pharmacological agent,
- incubating the mixture under conditions which, in the absence of the candidate pharmacological agent, permit a first amount of phosphorylation of the pathway specific Smad polypeptide by the TGF-β superfamily receptor complex or the activated TGFβ superfamily type I receptor, and
- detecting a test amount of phosphorylation of the pathway specific Smad polypeptide by the TGF-β superfamily receptor complex or the activated TGFβ superfamily type I receptor, wherein reduction of the test amount of the phosphorylation of the pathway specific Smad polypeptide relative to the first amount of the phosphorylation of the pathway specific Smad polypeptide indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which enhances the TGF-β superfamily signal transduction inhibitory activity of Smad7 and wherein increase of the test amount of the phosphorylation of the pathway specific Smad polypeptide relative to the first amount of the phosphorylation of the pathway specific Smad polypeptide indicates that the candidate pharmacological agent is a lead compound for a pharmacological agent which disrupts the TGF-β superfamily signal transduction inhibitory activity of Smad7.
Dependencies are inferred from the claim text.