44 results about "Melanocortin 1 receptor" patented technology

Linear and cyclic peptidomimetics which bind to one or more melanocortin receptors are provided, which peptidomimetics include at least one ring-constrained amino acid surrogate of formula I:where R1, R2, R3, R4, R5, R6, R7, R8, and y are as defined in the specification, together with methods for synthesizing ring-constrained amino acid surrogates of formula I and peptidomimetics incorporating the same, and methods of use of peptidomimetics in the treatment of various diseases, syndromes and conditions.

Melanocortin receptor-specific compounds with diamine groups of the general formulaand pharmaceutically acceptable salts thereof, where W is a diamine heteroatom unit with at least one cationic center, hydrogen bond donor or hydrogen bond acceptor, J, Q, L1, L2, L3, R1a, R1b, R2a, R2b and X are as defined in the specification, and the carbon atom marked with an asterisk can have any stereochemical configuration. Compounds disclosed herein bind to one or more melanocortin receptors and may be an agonist, a partial agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist as to one or more melanocortin receptors, and may be employed for treatment of one or more melanocortin receptor-associated conditions or disorders, including specifically treatment of obesity and related conditions.

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.

The present invention is directed to a compound according to formula,(R2R3)-B1-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-A11-A12-A13-B2-B3-R1, that act as ligands for one or more of the melanocortin receptors, the pharmaceutically-acceptable salts thereof, to methods of using such peptides to treat mammals and to pharmaceutical compositions useful therefore comprising said peptides.

Short tri- and tetrapeptides according to the following Formula I Ar(CH2)mX1—X2—CO—X3—X4—X5-(Trp)n-NX6R are potent, selective agonists of melanocortin 1 receptor (MC1R). Provided herein are skin care compositions including Formula I peptide agonists of MC1R and methods of regulating a skin condition of a mammal that include applying to a treatment surface of the body a safe and effective amount of a skin care composition including a Formula I peptide. The peptides, skin care compositions, and skin care methods described herein are useful in regulating a skin condition of a mammal associated with exposure ultraviolet (UV) radiation, including sunburn, UV sensitivity, photoaging, and skin pigmentation, particularly in the absence of sun exposure.

The present invention provides compounds of Formula (I) that are useful for binding and / or modulating the biological activity of the melanocortin-1 receptor (MC1R). Compounds of this invention can be used to treat diseases and / or conditions in which modulation of MC1R is beneficial. Such diseases and / or conditions include, but are not limited to, hyperpigmentation (including melasma), hypopigmentation (including vitiligo), melanoma, basal cell carcinoma, squamous cell carcinoma, erythropoietic protoporphyria, polymorphous light eruption, solar urticaria, photosensitivity, sunburn, inflammatory diseases, aberrant fibroblast activity and pain.

The invention relates to methods of treatment comprising administering a compound of the general formula (1):to a patient or a healthy individual.

There is provided novel diazepines that function as agonists at the melanocortin 4 receptor and as agonists at the melanocortin 1 receptor, pharmaceutical compositions containing them, methods for their use in treatment, and processes for their preparation.

A melanocortin receptor agonist cyclic peptide of the formulawhere R, x and y are as defined in the specification, compositions and formulations including the peptide of the foregoing formula, and methods of preventing, ameliorating or treating melanocortin receptor-mediated diseases, indications, conditions and syndromes, including sexual dysfunction such as male erectile dysfunction and female sexual dysfunction.

The present invention relates to methods for predicting, diagnosing and monitoring skin states and skin diseases. The methods combine the use of non-invasive skin collecting techniques with one or more assays for determining mitochondrial DNA (mtDNA) aberrations and Melanocortin 1 Receptor (MC1R) variants, thereby providing a comprehensive tool for identifying, predicting and / or monitoring photoageing, ultraviolet radiation (UVR) damage or skin disease. The methods of the invention may also be effective in screening for new therapeutic agents, skin care products and treatment regimes, and may also be useful for monitoring the response of a subject to a preventative or therapeutic treatment.

The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I)or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and / or energy balance and body weight related diseases, disorders and / or conditions, including obesity, overweight and diseases, disorders and / or conditions associated with obesity and / or overweight, such as type 2 diabetes and metabolic syndrome.

The present invention relates to melanocortin receptor agonists of formula (I), which is useful in the treatment of obesity, diabetes and male and / or female sexual dysfunction

Disclosed are biological markers for obesity and methods for diagnosing and treating obesity and related conditions by detecting and modulating the activity of auto-antibodies against the melanocortin-4 receptor or a portion of the melanocortin-4 receptor. Also disclosed are methods for discovering new therapeutics which modulate the activity of auto-antibodies against the melanocortin-4 receptor or a portion of the melanocortin-4 receptor, in particular which prevent the binding of auto-antibodies against the melanocortin-4 receptor or a portion of the melanocortin-4 receptor.

A MC1R peptide ligand-elastic vesicle complex for preventing skin maladies. The MC1R peptide ligand is modified by coupling the melanocortin 1 receptor (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 patch or viscous emulsion that can be applied to human skin.

Disclosed are monoclonal antibodies, binding fragments, and derivatives thereof directed to the human melanocortin-4 receptor, as well as pharmaceutical compositions including the same, and therapeutic uses, including methods for treating cachexia and related conditions and diseases, using such monoclonal antibodies, binding fragments, derivatives, and pharmaceutical compositions.

Disclosed are novel ligands based on an AGRP template that can rescue endogenous melanocortin agonist and / or antagonist dysfunction at MCR polymorphisms. In particular, the present invention provides novel synthetic ligands based on AGRP templates that can rescue endogenous melanocortin agonist dysfunction at MC4R polymorphisms to treat children and adults with these mutations and increase their quality of life.

A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radio labeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa1-Xaa2a-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7a (I) or Xaa1-Xaa2b-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7b (II). Xaa1 is L- / D-Nle, L- / D-Nle, L- / D-Ala, L- / D-Leu, L- / D-Ile, D-Ile, L- / D-Cys, L- / D-Met, L- / D-Phe, L- / D-Trp, L- / D-Val, L- / D-Nal, L- / D-2-Nal, Gly, L- / D-α-aminobutryic acid, L- / D-norvaline, or L- / D-homonorleucine. Xaa2a and Xaa7b are L- / D-Cys, L- / D-Asp, L- / D-Glu, L- / D-2-Aad, L- / D-3-Aad, L- / D-Pra, L- / D-Hpg, or L- / D-Bpg. Xaa2b and Xaa7a are L- / D-Cys, L- / D-Lys, L- / D-Orn, L- / D-Dab, L- / D-Dap, L- / D-Lys(N3), L- / D-Orn(N3), L- / D-Dab(N3), L- / D-Dap(N3), L- / D-2-(5′-azidopentyl)alanine, or L- / D-2-(6′-azidohexyl)alanine. Xaa3 is L- / D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-alanine. Xaa4 is L- / D-Phe, L- / D-2-Nal, L- / D-Phe(4-F), L- / D-Phe(4-Cl), L- / D-Phe(4-Br), L- / D-Phe(4-I), L- / D-Phe(4-NH2), or L- / D-Phe(4-NO2). Xaa5 is L- / D-Arg, L- / D-hArg), Leu, L- / D-Agb, or L- / D-Agp. Xaa6 is L- / D-Trp, L- / D-Phe, L- / D-Trp(5-Br), L- / D-Trp(5-OCH3), L- / D-Trp(6-F), L- / D-Trp(5-OH) or L- / D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa3, Xaa5, Xaa6 and Xaa7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa3, Xaa5, Xaa6 and Xaa7b is alpha N-methylated. The linker comprises an albumin-binding group.

A method for inducing melanogenesis in a human subject having a melanocortin 1 receptor (MC1R) variant allele associated with loss of or diminished receptor function comprises administering to said subject an amount of an α-melanocyte stimulating hormone (α-MSH) analogue effective to induce melanogenesis by the melanocytes in the skin or other epidermal tissue of the subject.

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.

A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radiolabeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa1-Xaa2a-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7a (I) or Xaa1-Xaa2b-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7b (II). Xaa1 is L- / D-Nle, L- / D-Nle, L- / D-Ala, L- / D-Leu, L- / D-Ile, D-Ile, L- / D-Cys, L- / D-Met, L- / D-Phe, L- / D-Trp, L- / D-Val, L- / D-Nal, L- / D-2-Nal, Gly, L- / D-α-aminobutryic acid, L- / D-norvaline, or L- / D-homonorleucine. Xaa2a and Xaa7b are L- / D-Cys, L- / D-Asp, L- / D-Glu, L- / D-2-Aad, L- / D-3-Aad, L- / D-Pra, L- / D-Hpg, or L- / D-Bpg. Xaa2b and Xaa7a are L- / D-Cys, L- / D-Lys, L- / D-Orn, L- / D-Dab, L- / D-Dap, L- / D-Lys(N3), L- / D-Orn(N3), L- / D-Dab(N3), L- / D-Dap(N3), L- / D-2-(5′-azidopentyl)alanine, or L- / D-2-(6′-azidohexyl)alanine. Xaa3 is L- / D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-N alanine. Xaa4 is L- / D-Phe, L- / D-2-Nal, L- / D-Phe(4-F), L- / D-Phe(4-Cl), L- / D-Phe(4-Br), L- / D-Phe(4-I), L- / D-Phe(4-NH2), or L- / D-Phe(4-NO2). Xaa5 is L- / D-Arg, L- / D-hArg), Leu, L- / D-Agb, or L- / D-Agp. Xaa6 is L- / D-Trp, L- / D-Phe, L- / D-Trp(5-Br), L- / D-Trp(5-OCH3), L- / D-Trp(6-F), L- / D-Trp(5-OH) or L- / D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa3, Xaa5, Xaa6 and Xaa7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa3, Xaa5, Xaa6 and Xaa7b is alpha N-methylated. The linker comprises an albumin-binding group.