Abstract: Provided herein are small molecule agonists of the apelin receptor for the treatment of disease. The compounds disclosed herein are useful for the treatment of a range of cardiovascular, renal and metabolic conditions. The present invention is based on the seminal discovery of a series of potent small molecule agonists of the apelin receptor, which are useful for the treatment of diseases including heart failure, chronic kidney disease, hypertension, and metabolic disorders such as insulin resistance/diabetes and obesity. The compounds disclosed herein are highly specific for the apelin receptor versus the angiotensin II receptor (ATI).

Abstract: Provided herein are compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Abstract: Disclosed are compositions and methods for treatment of atherosclerosis and atherosclerotic plaques. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerosis. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerotic plaques. In particular, compositions comprising a plaque-homing element, a CendR-activating element, and a plaque-inhibiting element are disclosed.

Abstract: Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Abstract: Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper-mineralization.

Abstract: Using 3D printing, a microwell is formed by providing a plurality of masks, each mask representing a cross-section of a layer of the concave structure. Progressive movement of a projection plane exposes a pre-polymer solution to polymerizing radiation modulated by the masks to define the layers of the microwell, where each layer is exposed for a non-equal exposure period as determined by a non-linear factor. In a preferred embodiment, a first portion of the masks are base layer masks, which are exposed for a longer period than subsequent exposure periods. Shapes of the microwells, which may include circular, square, annular, or other geometric shapes, and their depths, are selected to promote aggregation behavior in the target cells, which may include tumor cells and stem cells.

Abstract: The present specification discloses APY cyclic peptides having EphA4 antagonistic activity, pharmaceutical compositions containing such EphA4 antagonists, and methods and uses of treating an EphA4-based disease, disorder or pathology in an individual using such APY cyclic peptides or pharmaceutical compositions.

Abstract: Provided herein is the use of compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), alone or in combination with other therapeutic agents, in the treatment of human immunodeficiency virus (HIV). Described herein is the use of IAP antagonists in the treatment of human immunodeficiency virus (HIV) in a mammal, alone or in combination with other therapeutic agents used in HIV therapy. In one aspect, provided herein is a method of treating human immunodeficiency virus (HIV) in an individual in need thereof comprising administering a therapeutically effective amount of at least one inhibitor of apoptosis proteins (IAP) antagonist.

Abstract: Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.

Abstract: In certain aspects, the invention provides a method for treating a disease or condition in a subject, the method comprising co-administering to a subject in need thereof a therapeutically effective amount of at least one ULK1-inhibiting pyrimidine, and a therapeutically effective amount of an mTOR inhibitor.

Abstract: The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the formula (I): wherein R1 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R2 and R3 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R4 and R5 are the same or different and each represent a hydrogen atom, an optionally substituted C1-6 alkyl group, or the like, R6 represents a hydrogen atom or the like, each R7 may be the same or different and may each represent an optionally substituted C1-6 alkoxy group or the like, X represents —CH?, —C(—R7)?, or —N?, and m represents 1 to 4, or a pharmacologically acceptable salt thereof.

Abstract: The present specification discloses APY cyclic peptides having EphA4 antagonistic activity, pharmaceutical compositions containing such EphA4 antagonists, and methods and uses of treating an EphA4-based disease, disorder or pathology in an individual using such APY cyclic peptides or pharmaceutical compositions.

Abstract: Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.

Abstract: Provided herein are biomolecule conjugates, and methods of use thereof, wherein the conjugate comprises a cytokine, typically an immunopotentiating cytokine, and a peptide comprising or consisting of the sequence CSGRRSSKC (SEQ ID NO:1). Biomolecule conjugates of the invention find application, inter alia, in the treatment of turnouts, atherosclerosis and fibrosis, and the degradation of ECM associated therewith. Also provided herein are uses of a peptide comprising or consisting of the sequence of SEQ ID NO:1, optionally linked to a delectable agent and/or a carrier, in the detection and/or localisation of tumour, atherosclerotic and fibrotic tissue.

Abstract: Disclosed are recombinant polypeptides that include human TRAIL sequences as well as human leucine zipper motifs as well as polynucleotides that encode the recombinant polypeptides, expression vectors that comprise the polynucleotides, pharmaceutical compositions comprising the polypeptides, and methods of using the pharmaceutical compositions for the treatment of cancer. Further disclosed are TRAIL sequences with stabilizing mutations and methods of expressing the disclosed polypeptides in E. coli.

Abstract: Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Abstract: Disclosed are compositions and methods for treatment of atherosclerosis and atherosclerotic plaques. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerosis. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerotic plaques. In particular, compositions comprising a plaque-homing element, a CendR-activating element, and a plaque-inhibiting element are disclosed.

Abstract: Disclosed are methods and compositions for selectively targeting sites of traumatic brain injury (TBI). A brain injury-specific 4-amino acid peptide (sequence CAQK), identified by in vivo phage display screening in mice with acute brain injury, shows selective binding to mouse and human brain injury lesions, and when systemically injected, specifically homes to sites of injury in penetrating and non-penetrating (controlled cortical impact) brain injury models. Also disclosed are methods and compositions for delivering therapeutic compounds to such sites. CAQK-coated nanoparticles containing silencing oligonucleotides provide an alternative to local delivery of therapeutics, which is invasive and can add complications to the injury.

Abstract: Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenviroment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

Abstract: Provided herein are small molecule Fatty Acid Synthase Inhibitors, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.