Abstract: Peptide analogues of ?-amyloid and methods of using said analogues for neuroprotection are described herein. The ?-amyloid peptide analogues have a sequence that is at least 50% identical to an N-terminal ?-amyloid core fragment. A pharmaceutical composition of the ?-amyloid peptide analogues in a pharmaceutically acceptable carrier can be administered to a subject for neuromodulation. The ?-amyloid peptide analogues, while lacking neurotoxicity, effectively provides for protective activity against ?-amyloid toxicity.

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: Compositions and methods for treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described herein. A therapeutically effective amount of a composition comprising a melanocortin 5 receptor (MC5R) peptide ligand according to the following: in a pharmaceutically acceptable carrier is administered to the subject. Xaa can be Cha or Pro. The MC5R peptide is a selective MC5R antagonist, and administration thereof to the subject can treat the depressive or anxiety disorder with clinical improvement observed in a relatively short time.

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: Ligand-drug conjugates for targeted melanoma therapies are disclosed herein. A ligand is conjugated to a cytotoxic cancer drug through a cleavage linker. The ligand can bind to an overexpressed receptor on a cancer cell, resulting in selectivity. This allows the drug to enter a cancer cell selectively and release the drug within that specific cancer cell. Such therapies provide selectivity to melanoma through a ligand that targets the MC1R receptor, which is highly expressed in 80% of malignant melanomas. The ligand-drug conjugates can be used to deliver a wide range of cytotoxic cancer drugs selective to melanoma cells which may solve the drug resistance problem of melanoma in current therapies.

Abstract: The present invention relates generally to a compound having both agonist activity at opioid receptor(s) and antagonist activity at NK1 receptor, and methods for producing and using the same. This combination of activities provides several synergistic and/or beneficial effects such as enhanced potency in analgesic effect and reduction or inhibition of tolerance.

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 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: 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)nCH3, 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: 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) are for the treatment of pain. The ORLs comprise peptide portions that are analogs derived from enkephalins, endomorphins, or [DArg2, Lys4]-dermorphine (DALDA), as well as tail portions that comprise a lipophilic molecule such as a 4-anilidopiperidine moiety.

Abstract: Compositions and methods for treating a depressive disorder or an anxiety disorder in a subject in need of such treatment are described herein. A therapeutically effective amount of a composition comprising a melanocortin 5 receptor (MC5R) peptide ligand according to the following: in a pharmaceutically acceptable carrier is administered to the subject. Xaa can be Cha or Pro. The MC5R peptide is a selective MC5R antagonist, and administration thereof to the subject can treat the depressive or anxiety disorder with clinical improvement observed in a relatively short time.

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: 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 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: 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 melanocortin 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: 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: 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)nCH3, or —CO—(CH2)nCF3 with n ranging from 1 to 6. R2 can be an —CONH2, —COON, or —CH2OH. Xaa, Yaa, and Zaa can each be a natural amino acid or an unnatural amino acid.

Abstract: Described are Dynorphin A analog compounds and uses thereof for treating pain in humans and lower animals by administering to a human or lower animal in need of treatment. The compounds interact with the bradykinin receptor to relieve pain. Preferred compounds are amphipathic [Des-Arg7]-dynorphin A peptide analogs and specific cyclic dynorphin A peptide analogs.

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 a melanocortin 5 receptor (MC5R) peptide ligand according to SEQ NO. 1: in a pharmaceutically acceptable carrier is administered to the subject. Xaa can be Cha or Pro. The MC5R peptide is a selective MC5R antagonist, and administration thereof to the subject can treat the depressive or anxiety disorder with clinical improvement observed in a relatively short time.

Abstract: Peptide analogues of ?-amyloid and methods of using said analogues for neuroprotection are described herein. The ?-amyloid peptide analogues have a sequence that is at least 50% identical to an N-terminal ?-amyloid core fragment. A pharmaceutical composition of the ?-amyloid peptide analogues in a pharmaceutically acceptable carrier can be administered to a subject for neuromodulation. The ?-amyloid peptide analogues, while lacking neurotoxicity, effectively provides for protective activity against ?-amyloid toxicity.