Abstract: A backbone N-methylation approach on SHU9119, a non-selective cyclic peptide antagonist at hMC3R and hMC4R. Systematic N-methylated derivatives of SHU9119, with all possible backbone N-methylation combinations have been synthesized and examined for their binding and functional activities towards melanocortin receptor subtypes 1, 3, 4 and 5 (hMCRs). Several N-methylated analogues, which have selective and potent agonists or antagonists activity for the hMC1R or hMC5R or selective antagonist activity for the hMC3R, are discovered from the library. The selective hMC1R ligands show strong binding for human melanoma cells. The first universal antagonist for all subtypes of hMCRs will be of critical importance to modulate the melanocortin system with endogenous agonists.

Abstract: The present invention provides a compound of the formula: wherein ring Z is a 5-, 6- or 7-membered ring; R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aralkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heteroaralkyl; R2 is C1-10 alkylene; and Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(?O)—X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. The present invention also provides a method for using compound of Formula I to treat a wide variety of clinical conditions.

Abstract: A gamma-melanocyte stimulating hormone (?-MSH) derivative having improved stability, selectivity and bioavailabilty. The ?-MSH derivative is selective for the melanocortin-1 receptor (MC1 R) and is deliverable to skin cells via topical or transdermal delivery. The ?-MSH derivative is made up of naturally occurring amino acids for stimulating melanin from within for photoprotection of human skin against ultraviolet radiation damage.

Abstract: Compositions and methods of treating a central nervous system (CNS) disorder or mood disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising a melanocortsn 5 receptor (MC5R) peptide ligand in a pharmaceutically acceptable carrier is administered to the subject. The MCSR peptide ligand is a selective MCSR antagonist, in which administration thereof to the subject can treat the CNS disorder or mood disorder with clinical improvement observed in a relatively short time.

Abstract: Compositions and methods for treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising compound PG-20N in a pharmaceutically acceptable carrier is described. According to another embodiment, the subject disclosure features method of treating a depressive disorder or an anxiety disorder in a subject in need of such treatment. The method may comprise administering to the subject a therapeutically effective amount of a composition comprising PG-20N.

Abstract: The present invention provides using a substituted 1-arylalkyl-4-acylaminopiperidine compound of Formula I: to treat various clinical conditions including, but not limited to, hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy, epithelial wounds, herpes zoster infection, or opioid-induced pruritus. In compound of Formula I, R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is C1-6 alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(?O)—X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl.

Abstract: A gamma-melanocyte stimulating hormone (?-MSH) derivative having improved stability, selectivity and bioavailabilty. The ?-MSH derivative is selective for the melanocortin-1 receptor (MC1 R) and is deliverable to skin cells via topical or transdermal delivery. The ?-MSH derivative is made up of naturally occurring amino acids for stimulating melanin from within for photoprotection of human skin against ultraviolet radiation damage.

Abstract: Opioid receptor ligands (ORLs) that are multifunctional having agonist activity at mu opioid receptor (MOR), agonist activity at delta opioid receptor (DOR), and antagonist (or partial agonist) activity at kappa opioid receptor (KOR). The ORLs comprise peptide portions that are analogs derived from enkephalins, EM-1, or DALDA, as well as tail portions that comprise a lipophilic molecule such as a 4-anilidopiperidine moiety.

Abstract: The present invention provides a compound of the formula: wherein ring Z is a 5-, 6- or 7-membered ring; R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aralkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heteroaralkyl; R2 is C1-10 alkylene; and Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(?O)-X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. The present invention also provides a method for using compound of Formula I to treat a wide variety of clinical conditions.

Abstract: Methods of treating a central nervous system (CNS) disorder or mood disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising a melanocortin 5 receptor (MC5R) peptide ligand in a pharmaceutically acceptable carrier is administered to the subject. The MC5R peptide ligand is a selective MC5R antagonist, in which administration thereof to the subject can treat the CNS disorder or mood disorder with clinical improvement observed in a relatively short time.

Abstract: Methods of treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising Ac-Nle4-c[Asp5-His6-(NMe)D-Nal(2?)7-Arg8-Trp9-(NMe)Lys10]-NH2 (PEPTIDE 9), in a pharmaceutically acceptable carrier is administered to the subject. PEPTIDE 9 is a selective MC5R antagonist, in which administration thereof to the subject can treat the depressive or generalized anxiety disorder with clinical improvement observed in a relatively short time.

Abstract: The invention provides compounds that bind with high affinities to the ?-, ?- and ?-opioid receptors and ?2-adrenoreceptor. In addition to providing these compounds with novel pharmacological binding properties, the invention also describes detailed novel methods for the preparation of representative compounds and a scheme for the synthesis of related compounds that bind to the opioid receptors and/or ?2-adrenoreceptor.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: Methods of treating a central nervous system (CNS) disorder or mood disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising a melanocortin 5 receptor (MC5R) peptide ligand in a pharmaceutically acceptable carrier is administered to the subject. The MC5R peptide ligand is a selective MC5R antagonist, in which administration thereof to the subject can treat the CNS disorder or mood disorder with clinical improvement observed in a relatively short time.

Abstract: Modulators of melanocortin receptors (MCR) are provided herein. An MC5R peptide ligand is represented by to Formula 1: R1-Nle4-c[Xaa5-Yaa6-(NMe)D-Nal(2?)7-Arg8-Trp9-(NMe)Zaa10]-R2. R1 can be an acetyl, a glycosylated amino acid, —CO—(CH2)n—CH3, or ?CO—(CH2)nCF3 with n ranging from 1 to 6. R2 can be an —CONH2, —COOH, or —CH2OH. Xaa, Yaa, and Zaa can each be a natural amino acid or an unnatural amino acid.

Abstract: Methods of treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described. A therapeutically effective amount of a composition comprising Ac-Nle4-c[Asp5-His6-(NMe)D-Nal(2?)7-Arg8-Trp9-(NMe)Lys10]-NH2 (PEPTIDE 9), in a pharmaceutically acceptable carrier is administered to the subject. PEPTIDE 9 is a selective MC5R antagonist, in which administration thereof to the subject can treat the depressive or generalized anxiety disorder with clinical improvement observed in a relatively short time.

Abstract: A melanocortin 1 receptor (MC1R) peptide ligand-elastic vesicle complex. The MC1R peptide ligand is modified by coupling the MC1R ligand to a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, elastic vesicles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The MC1R peptide ligand-elastic vesicle complex is prepared as a topical formulation.

Abstract: A compound for treatment of pain comprising a single multivalent/multifunctional ligand with agonist activity at opioid receptors and with antagonist activity at NK-1 receptors, joined by a linker. Also disclosed is a pharmaceutical compound comprising the above compound in a pharmaceutically acceptable carrier.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: A melanocortin 1 receptor (MC1R) peptide ligand-elastic vesicle complex. The MC1R peptide ligand is modified by coupling the MC1R ligand to a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, elastic vesicles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The MC1R peptide ligand-elastic vesicle complex is prepared as a topical formulation.