A hetero-targeted, dual-responsive nanogel to deliver chemotherapeutic agents to a metastatic cancer is provided. The nanogel includes a first chemotherapeutic agent, a second chemotherapeutic agent, a first targeting ligand, and a second targeting ligand. A method of treating cancer in a mammal with the nanogel are also provided.

A hetero-targeted, dual-responsive nanogel to deliver chemotherapeutic agents to a metastatic cancer is provided. The nanogel includes a first chemotherapeutic agent, a second chemotherapeutic agent, a first targeting ligand, and a second targeting ligand. A method of treating cancer in a mammal with the nanogel are also provided.

A hetero-targeted, dual-responsive nanogel to deliver chemotherapeutic agents to a metastatic cancer is provided. The nanogel includes a first chemotherapeutic agent, a second chemotherapeutic agent, a first targeting ligand, and a second targeting ligand. A method of treating cancer in a mammal with the nanogel are also provided.

The subject invention concerns peptide mimetics of SOCS proteins and methods of use. In one embodiment, a peptide mimetic of the invention binds to a SOCS1 and a SOCS3 target protein. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51, or a functional fragment or variant thereof. In a further embodiment, a peptide of the invention can comprise multiple copies of the mimetic sequence. In one embodiment, a peptide of the invention comprises two or more copies of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:3 and/or SEQ ID NO:4 to and/or SEQ ID NO:52, or a functional fragment or variant thereof. The subject invention also pertains to methods of treating and/or preventing autoimmune conditions and/or disorders. In one embodiment, one or more peptide mimetics of the invention are used to treat an autoimmune condition or disorder in a person or animal. In a specific embodiment, a mimetic of the invention is used to treat SLE in a person or animal. The subject invention also concerns methods for diagnosing and/or monitoring progression of SLE in a person or animal.

The subject invention concerns peptide mimetics of SOCS proteins and methods of use. In one embodiment, a peptide mimetic of the invention binds to a SOCS1 and a SOCS3 target protein. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51, or a functional fragment or variant thereof. In a further embodiment, a peptide of the invention can comprise multiple copies of the mimetic sequence. In one embodiment, a peptide of the invention comprises two or more copies of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:3 and/or SEQ ID NO:4 to and/or SEQ ID NO:52, or a functional fragment or variant thereof. The subject invention also pertains to methods of treating and/or preventing autoimmune conditions and/or disorders. In one embodiment, one or more peptide mimetics of the invention are used to treat an autoimmune condition or disorder in a person or animal. In a specific embodiment, a mimetic of the invention is used to treat SLE in a person or animal. The subject invention also concerns methods for diagnosing and/or monitoring progression of SLE in a person or animal.

The subject invention concerns peptide mimetics of SOCS proteins and methods of use. In one embodiment, a peptide mimetic of the invention binds to a SOCS1 and a SOCS3 target protein. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51, or a functional fragment or variant thereof. In a further embodiment, a peptide of the invention can comprise multiple copies of the mimetic sequence. In one embodiment, a peptide of the invention comprises two or more copies of SEQ ID NO:1 and/or SEQ ID NO:2 and/or SEQ ID NO:51. In a specific embodiment, a peptide mimetic of the invention comprises the amino acid sequence of SEQ ID NO:3 and/or SEQ ID NO:4 to and/or SEQ ID NO:52, or a functional fragment or variant thereof. The subject invention also pertains to methods of treating and/or preventing autoimmune conditions and/or disorders. In one embodiment, one or more peptide mimetics of the invention are used to treat an autoimmune condition or disorder in a person or animal. In a specific embodiment, a mimetic of the invention is used to treat SLE in a person or animal. The subject invention also concerns methods for diagnosing and/or monitoring progression of SLE in a person or animal.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

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and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):

##STR00001##

and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The instant invention relates to combinations of the compound of formula (I) or pharmaceutically acceptable salts thereof with other active pharmaceutical ingredients (I), pharmaceutical compositions comprising them, and their use as medicaments, particularly for the treatment of hematological malignancies.

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The instant invention relates to combinations of the compound of formula (I) or pharmaceutically acceptable salts thereof with other active pharmaceutical ingredients (I), pharmaceutical compositions comprising them, and their use as medicaments, particularly for the treatment of hematological malignancies.

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