Abstract: The present disclosure relates to peptide having a sequence comprising: (SEQ?ID?NO:?1) Z1X1X2X3X4X5X6X7X8X9X10X11X12-NH2, and to their isomers, pharmaceutically acceptable salts, or prodrugs thereof, methods of use, and methods for their preparation. The peptides disclosed herein are useful for modulating orexin receptor activity and may be used in the treatment of disorders in which orexin receptor activity is implicated, such as narcolepsy, a hypersomnia disorder, a neurodegenerative disorder, a symptom of a rare genetic disorder, a mental health disorder, a metabolic syndrome, osteoporosis, cardiac failure, coma, or a complication in emergence from anaesthesia.

Abstract: Provided herein are melanocortin 3 receptor (MC3R) agonist peptides and methods of use thereof for the treatment and/or prevention of eating disorders (e.g., anorexia nervosa, cachexia, etc.), metabolic disorders (e.g., sarcopenia), endocrine and growth disorders (e.g. delayed growth and/or delayed puberty), and/or emotional/mental disorders (e.g., depression, anxiety, OCD, PTSD, etc.). In particular, provided herein are MC3R agonist peptides that exhibit enhanced selectivity for MC3R over other melanocortin receptors (e.g., melanocortin 4 receptor (MC4R), melanocortin 1 receptor (MC1R), etc.) and/or are MC4R antagonists, and methods of use thereof. MC3R agonist peptides herein may exhibit enhanced in vitro potency, in vivo efficacy and pharmacokinetic properties compared to other know MC3R agonists.

Abstract: Disclosed are polypeptides, compositions, and methods useful for activating a glucagon-like peptide-1 (GLP-1) receptor and treating or preventing diseases or disorders at least partially mediated by glucagon-like peptide 1 (GLP-1).

Abstract: Among other things, the present disclosure provides agents that can bind to viruses such as SARS-CoV-2 and/or cells infected thereby. In some embodiments, the present disclosure provides methods for preventing and/or treating conditions, disorders or diseases associated with SARS-CoV-2 infection. In some embodiments, the present disclosure provides methods for preventing and/ or treating COVID-19.

Abstract: The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Abstract: The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Abstract: Disclosed are conjugates, comprising a peptide moiety, a linker, and an active moiety. Also disclosed are methods of using the conjugates for treating a disease, inducing antigen-specific immunotolerance to the active moiety, or extending the half-life of the active moiety.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Abstract: The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Abstract: Disclosed are polypeptides, compositions, and methods useful for activating a glucagon-like peptide-1 (GLP-1) receptor and treating or preventing diseases or disorders at least partially mediated by glucagon-like peptide 1 (GLP-1).

Abstract: Peptidomimetic macrocycles that comprise all-D configuration ?-amino acids and bind mouse double minute 2 (MDM2 aka E3 ubiquitin-protein ligase) and MDMX (aka MDM4) are described. These all-D configuration ?-amino acid peptidomimetic macrocycles are protease resistant, cell permeable without inducing membrane disruption, and intracellularly activate p53 by binding MDM2 and MDMX thereby antagonizing MDM2 and MDMX binding to p53. These peptidomimetic macrocycles may be useful in anticancer therapies, particularly in combination with chemotherapy or radiation therapy.

Abstract: This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Abstract: Disclosed are peptidomimetic macrocycles comprising a helix, such as an alpha helix, and methods of using such macrocycles for the treatment of disease such as cancer. In other aspects, the peptidomimetic macrocycle comprises an ?,?-disubstituted amino acid, or may comprise a crosslinker linking the ?-positions of at least two amino acids or at least one of said two amino acids may be an ?,?-disubstituted amino acid. Further included is the targeting of components of the Wnt signaling pathway such as the Tcf4-/3-catenin complex.

Abstract: The present invention provides biologically active peptidomimetic macrocycles for the treatment of cell proliferative disorders such as cancer and immunoproliferative disease.

Abstract: Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.