Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

##STR00001##

The present invention provides a peptide exhibiting melanogenesis promoting activity. A peptide according to the present invention increases the activity and expression of tyrosinase and the expression of factors involved in melanogenesis, thereby exhibiting an outstanding effect on melanogenesis. The peptide of the present invention can be used for the prevention, alleviation, and treatment of hypomelanosis. The outstanding activity and stability stated above allow the peptide of the present invention to be very favorably applied to medicines, quasi-medicines, and cosmetics.

Systems and methods for treatment of squamous cell carcinoma or other cancer utilizing targeting peptides are described. The targeting peptides interact with SCC cells or other cancerous cells to block or interfere with 14-3-3ε heterodimerization or CDC25A binding to 14-3-3ε. A peptide composition embodiment includes, but is not limited to, at least one of a first targeting peptide comprising a structure of Trp-Tyr-Trp-Lys-NH.sub.2 (SEQ ID NO: 1), a second targeting peptide comprising a structure of phospho-Ser178; Ac-Thr-Gln-Arg-Gln-Asn-Ser-(PO.sub.3.sup.2−)-Ala-Pro-Arg-Met-Leu-Ser-Ser-Asn-NH.sub.2 (SEQ ID NO: 2), and a third targeting peptide comprising a structure of phospho-Thr507 residue; Ac-Arg-Thr-Lys-Ser-Arg-Thr(PO.sub.3.sup.2−)-Trp-Ala-Gly-Glu-Lys-Ser-Lys-Arg-NH.sub.2 (SEQ ID NO: 3).

Provided are a polypeptide for tumor immunotherapy and use thereof. The polypeptide includes at least one polypeptide in a first peptide group, and optionally, at least one polypeptide in a second peptide group, the first peptide group includes polypeptides having amino acid sequences set forth in SEQ ID NO: 1 to SEQ ID NO: 6, and first derivative peptides thereof, and the second peptide group includes polypeptides having amino acid sequences set forth in SEQ ID NO: 7 to SEQ ID NO: 15, and second derivative peptides thereof. Further provided are an isolated nucleic acid, a construct, an expression vector, a host cell, a pharmaceutical composition, an antigen-presenting cell, an immune effector cell, a tumor vaccine, use of the polypeptide in the preparation of drugs for preventing or treating tumors, and a method for treating a patient suffering from tumors.

A method of treating a person with a substance abuse disorder, in particular, opioid abuse and psychostimulant abuse with a chemokine receptor antagonist pharmaceutical composition. The antagonist comprising five contiguous amino acids having the general structure: A-B-C-D-E in which A is Ser, Thr, Asn, Glu, or Ile; B is Ser, Thr, Asp, or Asn; C is Thr, Ser, Asn, Arg, or Trp; D is Tyr and E is Thr, Ser, Arg, or Gly. The amino acids are D stereoisomers. The method both relieves a person's symptoms and reduces the person's risks of addiction.

A method of treating a person with a substance abuse disorder, in particular, opioid abuse and psychostimulant abuse with a chemokine receptor antagonist pharmaceutical composition. The antagonist comprising five contiguous amino acids having the general structure: A-B-C-D-E in which A is Ser, Thr, Asn, Glu, or Ile; B is Ser, Thr, Asp, or Asn; C is Thr, Ser, Asn, Arg, or Trp; D is Tyr and E is Thr, Ser, Arg, or Gly. The amino acids are D stereoisomers. The method both relieves a person's symptoms and reduces the person's risks of addiction.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease encompassing chronic bronchitis, emphysema and remodeling of small airways that can be treated by the caveolin-1 peptide CSP7 (SEQ ID NO:1). Chronic tobacco smoke exposure (TSE)-induced lung injury includes increased alveolar and airway inflammation, type II alveolar epithelial cells (A.sub.2Cs) senescence and apoptosis, and mucus hypersecretion by AECs. Interleukin 17A-mediated induction of plasminogen activator inhibitor-1 (PAI-1) expression through caveolin-1 led to TSE-induced lung injury, which was abrogated by CSP7 treatment which abolished A.sub.2Cs senescence and apoptosis, and AECs mucus hypersecretion in TSE wild type (WT) mice. Ex vivo CSP7 treatment of lung tissue of COPD patients decreased A.sub.2C apoptosis and AEC mucus hypersecretion. Lung injury induced by PAI-1 expression in COPD lung tissue and WT mice (20 weeks TSE), with A.sub.2Cs senescence and apoptosis, and AEC mucus hypersecretion was abolished by CSP7.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease encompassing chronic bronchitis, emphysema and remodeling of small airways that can be treated by the caveolin-1 peptide CSP7 (SEQ ID NO:1). Chronic tobacco smoke exposure (TSE)-induced lung injury includes increased alveolar and airway inflammation, type II alveolar epithelial cells (A.sub.2Cs) senescence and apoptosis, and mucus hypersecretion by AECs. Interleukin 17A-mediated induction of plasminogen activator inhibitor-1 (PAI-1) expression through caveolin-1 led to TSE-induced lung injury, which was abrogated by CSP7 treatment which abolished A.sub.2Cs senescence and apoptosis, and AECs mucus hypersecretion in TSE wild type (WT) mice. Ex vivo CSP7 treatment of lung tissue of COPD patients decreased A.sub.2C apoptosis and AEC mucus hypersecretion. Lung injury induced by PAI-1 expression in COPD lung tissue and WT mice (20 weeks TSE), with A.sub.2Cs senescence and apoptosis, and AEC mucus hypersecretion was abolished by CSP7.

Methods of treating pruritis (e.g., associated with atopic dermatitis or psoriasis) are described. The methods can involve administering to a subject in need of treatment an antagonist of integrin α.sub.vβ.sub.3. The antagonist can block periostin-integrin signalling. The antagonist can be, for example, an antibody, a peptide having a RGD or SVD sequence, a peptidomimetic, an amine salt, a phosphoric acid salt, or a small molecule.

Methods of treating pruritis (e.g., associated with atopic dermatitis or psoriasis) are described. The methods can involve administering to a subject in need of treatment an antagonist of integrin α.sub.vβ.sub.3. The antagonist can block periostin-integrin signalling. The antagonist can be, for example, an antibody, a peptide having a RGD or SVD sequence, a peptidomimetic, an amine salt, a phosphoric acid salt, or a small molecule.