Abstract: Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

Abstract: Methods for treating or preventing tauopathies and/or A? amyloidosis by modulating CRF receptor signaling. Accumulation of hyperphosphorlyated tau protein in the CNS may be reduced by administration of CRF-R1 selective antagonists and/or CRF-R2 selective agonists. For example, in some aspects, methods for preventing the onset of Alzheimer's disease by administration of CRF-R1 selective antagonist are provided.

Abstract: Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

Abstract: Methods for treating or preventing tauopathies and/or A? amyloidosis by modulating CRF receptor signaling. Accumulation of hyperphosphorlyated tau protein in the CNS may be reduced by administration of CRF-R1 selective antagonists and/or CRF-R2 selective agonists. For example, in some aspects, methods for preventing the onset of Alzheimer's disease by administration of CRF-R1 selective antagonist are provided.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to b e identified receptor.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

Abstract: Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2? or ?. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn IL Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.

Abstract: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-? superfamily of polypeptide growth factors such that concentrations of ?10 nM of said polypeptide growth factor occupy ?50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-?, and other non-activin-like proteins.

Abstract: The present invention relates to a method for identifying modulators of B1 G-protein coupled receptors. The present invention also relates to a method for identifying an antagonist or agonist of the corticotropin-releasing factor receptor 2 (CRFR2). The present invention also relates to a method for improving antagonists or agonists of CRFR2. The present invention also relates to the three-dimensional structure of CRFR2 as representative of the B1 GPCR subfamily and its use as a basis for rational drug design of antagonist or agonists of B1 GPCRs.

Abstract: CRF peptide analogs that bind to CRFR1 with an affinity far greater than they bind to CRFR2. Some of these analogs exhibit CRF agonist activity. One exemplary analog that may be made by solid-phase synthesis is: (cyclo 31-34)[Ac-Pro4,D-Phe12,Nle18,21,Glu31,Lys34]-sucker urotensin(4-41).

Abstract: Methods for treating or preventing tauopathies and/or A? amyloidosis by modulating CRF receptor signaling. Accumulation of hyperphosphorlyated tau protein in the CNS may be reduced by administration of CRF-R1 selective antagonists and/or CRF-R2 selective agonists. For example, in some aspects, methods for preventing the onset of Alzheimer's disease by administration of CRF-R1 selective antagonist are provided.