Abstract: Methods of inhibiting the Hsp90 chaperone pathway including contacting one or more target cells with an effective amount of a naturally occurring beauvericin, a synthetic beauvericin, or a derivative, analog or prodrug, or a pharmacologically active salt thereof to reduce, decrease, or inhibit the Hsp90 chaperone pathway in the cells compared to a control are disclosed. The methods can reduce the viability of the target cells, for example, by increasing apoptosis or pro-apoptotic pathways. In preferred embodiments, the methods reduce or do not increase Hsp70, Hsp24, Hsp40, or HOP expression; reduce or do not increase the heat shock response; reduce or do not increase pro-survival pathways in the cells. Methods of treating diseases such as cancer, inflammatory diseases or disorders, neurodegenerative diseases, and infectious diseases using the disclosed compositions and methods are also disclosed.

Abstract: The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Abstract: The invention provides di-peptide conjugated antitumor agents, pharmaceutical compositions and methods for preparation and use thereof for treating various cancer and inflammation-related diseases and conditions. The present invention addresses the shortcomings of the existing anti-tumor and anti-inflammatory drugs, particularly in that the anti-tumor agents of the invention that selectively kill cancer cells with minimal damage to normal cells.

Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins that are degraded and/or otherwise inhibited by bifunctional compounds of the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand that binds to the ubiquitin ligase and on the other end a moiety that binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds of the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: The present invention relates to inhibitors of Nox1-dependent reactive oxygen species production and their use in the treatment of disorders associated with reactive oxygen species, such as hypertension and cancer.

Abstract: A polymer and a method for its preparation are provided. The polymer comprises poly(lactide), poly(lactide/glycolide) or poly(lactic acid/glycolic acid) segments bonded by ester linkages to both ends of an alkanediol core unit. The polymer is for use in a controlled release formulation for a medicament, preferably leuprolide acetate. The controlled release formulation is administered to a patient as a subcutaneous depot of a flowable composition comprising the polymer, a biocompatible solvent, and the medicament. Controlled release formulations comprising the polymer release leuprolide for treatment of prostate cancer patients over periods of 3-6 months.

Abstract: The present invention discloses peptides such as an isolated peptide consisting of an immunogenic HLA-A*2402-restricted epitope. For example, the isolated peptide may be selected from the group consisting of KYGVLLKTL (SEQ ID NO:11); RYMRQFVAL (SEQ ID NO: 12); RYVSRLLGI (SEQ ID NO: 13); RYGKGWDLL (SEQ ID NO: 14); RYLVQVQAL (SEQ ID NO: 15); and RYWELSNHL (SEQ ID NO: 16).

Abstract: The present invention is directed to peptide reagents, methods for detecting colon pre-cancer (dysplasia with non-polypoid or polypoid morphology) or cancer using the peptide reagents, and methods for targeting pre-cancerous or cancerous colon cells using the peptide reagents.

Abstract: N-acylpeptide derivatives are described. Compositions comprising N-acylpeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with tumors or cancers, immune, nervous, vascular, musculoskeletal, cutaneous system, or other tissues or systems in a subject.

Abstract: The present invention relates to a modified human tumor necrosis factor receptor-1 polypeptide which is capable of binding to a tumor necrosis factor in vivo or ex vivo, or to a fragment thereof. The modified human tumor necrosis factor receptor-1 polypeptide or the fragment thereof according to the present invention exhibit improved binding affinity to the tumor necrosis factor.

Abstract: The present invention relates to kinase inhibiting compositions and uses thereof. The invention further provides isolated kinase inhibiting peptides and uses thereof for inhibiting hyperplasia, for inhibiting the growth of neoplasms, and for inducing programmed cell death in a cell population.

Abstract: The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (?-, ?-)dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.

Abstract: Provided is a fusion protein comprising circularly permuted form of TRAIL, and the fusion protein contains circularly permuted form of TRAIL and oligopeptides located at the N-terminus and/or C-terminus of the permuted form. The oligopeptides contain a repeating sequence consisting of 3-10 histidines. The components of the circularly permuted form of TRAIL from N-terminus to C-terminus are: (a) amino acids 135-281 of TRAIL, (b) a linker, and (c) amino acids 121-135 of TRAIL or amino acids 114-135 of TRAIL or amino acids 95-135 of TRAIL or any fragments of amino acids 95-135 of TRAIL containing amino acids 121-135 of TRAIL. Also provided is a method for treating cancer by using the fusion protein.

Abstract: Provided herein are liposomal glycolipopeptidic vaccine formulations comprising an adjuvant and an immunogen for immunotherapy and/or treatment of cancer.

Abstract: The present invention relates to the compositions and use of compositions for treating a prostate condition in a subject. The use of composition comprises administering to the subject a subject effective amount of a pharmaceutical composition having a first agent that inhibits EN2 expression and/or EN2 activity and a second agent that inhibits PAX2 expression and/or PAX2 activity. The pharmaceutical composition may further comprise a third agent that enhances DEFB1 expression or activity.

Abstract: The present invention provides oligopeptides comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 4 and 5. The present invention also provides a pharmaceutical composition containing the amino acid sequence of selected from the group consisting of SEQ ID NOs: 3, 4 and 5 formulated for the treatment or prevention of cancer in a subject. Furthermore, the present invention provides a method of inducing immune response using such oligopeptides and pharmaceutical agents.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising said p97 fragments, and related methods of use thereof, for instance, to facilitate delivery of therapeutic or diagnostic agents across the BBB.

Abstract: The invention provides a molecule that inhibits or prevents an interaction between a Src family kinase and an androgen or estradiol receptor, for use in preventing or treating a non-cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject, or for use in preventing or treating a cancerous condition in which an activity of AR and/or ER is a contributory factor in a subject who wishes to preserve fertility, or for use in preventing or treating a gynaecological condition in which an activity of AR and/or ER is a contributory factor in a subject.

Abstract: Therapeutic peptides having guanylyl cyclase C agonist activity are disclosed. The therapeutic peptides are analogues of the E. coli STa peptide with non-natural amino acid, isosteric or D-amino acid substituents. The therapeutic peptides are useful in the treatment of chronic ideopathic constipation, inflammatory bowel disease, and other diseases. Pharmaceutical compositions comprising the therapeutic peptides are also disclosed.

Abstract: The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.

Abstract: N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject.

Abstract: The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.

Abstract: The invention relates to tumor therapy. In one aspect, the present invention relates to conjugates of an amatoxin and a target-binding moiety, e.g. an antibody, connected by certain linkages, which are useful in the treatment of cancer. In a further aspect the invention relates to pharmaceutical compositions comprising such conjugates.

Abstract: Base-labile crosslinkers, base-labile conjugates comprising such crosslinkers, methods of their synthesis and use are disclosed.

Abstract: MOTS3 is a novel polypeptide. Methods of treating diseases such as diabetes, obesity, fatty liver, and cancer using MOTS3 and pharmaceutical compositions thereof are disclosed herein.

Abstract: Disclosed herein are PACE4 inhibitors, compositions comprising PACE4 inhibitors and their uses thereof for lowering PACE4 activity, reducing cell proliferation, reducing tumor growth, reducing metastasis formation, preventing and/or treating cancer. Also provided are methods for lowering PACE4 activity, reducing the proliferation of a cell, reducing tumor growth and/or treating and preventing cancer. Methods for screening PACE4 inhibitors and cell proliferation inhibitors are further provided.

Abstract: The present disclosure provides isolated binding molecules that bind to human 4-1BB, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

Abstract: A method of using a Smac mimetic and pharmaceutical compositions thereof.

Abstract: Provided herein are compositions and kits comprising a therapeutic agent linked to a cleavable substrate, wherein the cleavable substrate is capable of being cleaved by cathepsin E. Also provided are methods of treating one or more symptoms of a disease or disorder characterized by expression of cathepsin E in a subject and methods of eliminating a cancer cell characterized by expression of cathepsin E using the provided compositions and kits. Further provided herein are methods of detecting the presence of a cancer cell or detecting a cathepsin E expressing cell using a photosensitizer linked to a cleavable substrate, wherein the cleavable substrate is capable of being cleaved by cathepsin E.

Abstract: The invention provides compositions and methods to treat cancer with an agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria (“an XTPP agent”) or a pharmaceutically acceptable salt thereof, an inhibitor of hydroperoxide metabolism and a pharmaceutically acceptable diluent or carrier.

Abstract: The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions thereof.

Abstract: Disclosed herein are compositions and methods for and involving selectively targeting tumor lymphatics.

Abstract: Compositions and pharmaceutical compositions including one or more selenium-containing COX-2 inhibitors are provided according to aspects of the present invention. Methods of treating a subject having or suspected of having cancer are provided according to aspects of the present invention which include administering a therapeutically effective amount of a pharmaceutical composition including a selenium-containing COX-2 inhibitor.

Abstract: The invention relates to compounds of Formula I: and pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, and R3 are defined as set forth in the specification. The compounds are agonists of neurotrophin (such as nerve growth factor) receptors.

Abstract: It is provided PACE4 inhibitors and their uses for treating infection, cancer. Particularly, it is provided a method or use for the treatment of a cancer in a subject, comprising administering to the subject a therapeutically effective amount of the PACE4 inhibitors or the composition disclosed.

Abstract: This invention describes a method for treating cancer by increasing the nuclear localization of the COMMD1 protein, which is associated with decreasing or blocking the proliferation of the cancer cell. The invention is also related to the use of agents that increase nuclear localization of the COMMD1 protein, in the manufacture of a medicament for cancer therapy. These agents can be peptides or proteins, among other compounds. The invention is also related to the optimization of a peptide, coming from the sequence HARIKPTFRRLKWKKYKGKFW, to increase the nuclear localization of the protein COMMD, and thus, to increase the antitumor effect of this peptide.

Abstract: The present invention relates to a Wnt5a protein or peptide thereof possessing Wnt5a signaling properties, such as Foxy5, for use in the treatment of prostate cancer, in particular in patients that have undergone or will undergo radical prosteatectomy. The invention also relates to a method for determining a prognosis for a patient having prostate cancer and a kit for performing said method. The method for determining a prognosis for a patient comprises the steps of: evaluating an amount of Wnt5a protein present in at least part of a sample earlier obtained from the patient and determining a sample value corresponding to the evaluated amount; comparing the sample value obtained in step a) with a reference value associated with a reference prognosis; and, if said sample value is higher than said reference value, concluding that the prognosis for said patient is better than said reference prognosis.

Abstract: Methods and pharmaceutical compositions for the treatment of cancer or acute ischemia are provided. Also provided are methods of identifying agents capable of preventing the formation of or dissociating the MSF-A-HIF-1alpha protein complex, and methods of determining the prognosis of an individual having cancer by identifying the presence or absence of such a protein complex.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and a method of treating cancer using the peptide.

Abstract: Disclosed are: a peptide comprising an amino acid sequence composed of contiguous nine amino acid residues derived from a WT1 protein, wherein an amino acid residue at position 2 in the amino acid sequence is selected from the group consisting of Ala, Ile, Leu, Val, Phe, Tyr, Ser and Asp and an amino acid residue at position 9 in the amino acid sequence is Arg; a polynucleotide encoding the peptide; a pharmaceutical composition comprising the peptide; and others.

Abstract: The invention is directed to methods of treating cancer by administration of heat shock protein 70 (Hsp70) to the subject suffering from cancer.

Abstract: Nanobiopolymeric conjugates based on biodegradable, non-toxic and non-immunogenic poly (?-L-malic acid) PMLA covalently linked to molecular modules that include morpholino antisense oligonucleotides (AONa), an siRNA or an antibody specific for an oncogenic protein in a cancer cell, and an antibody specific for a transferrin receptor protein, are provided. Methods for treating a cancer in subject with nanobiopolymeric conjugates are described.

Abstract: The invention provides a composition comprising SGEF protein or gene as a therapeutic means to clinical or subclinical defects associated with anomalies of at least one from among the macula, corpus callosum, hippocampus, liver or immune system and diseases including a feverless response to infection, a cancer or vision loss. Methods of diagnosis of such disease and development anomalies are based on detection of mutations of the SGEF gene or altered levels of the SGEF mRNA or protein. A change of at least about 20% in the level of expression visa-vie a normal individual indicates an SGEF anomaly. The SGEF protein is also used as a preventive or curative treatment of atherosclerosis by local or systemic delivery. The invention also provides a composition comprising an inhibitor of the SGEF gene expression or SGEF protein concentration, as a therapeutic means for glaucoma, osteoarthritis, auto-inflammatory diseases, tumors or cancers.

Abstract: Binding agents that modulate the immune response are disclosed. The binding agents may include soluble receptors, polypeptides, and/or antibodies. Also disclosed are methods of using the binding agents for the treatment of diseases such as cancer.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.

Abstract: Described herein are methods to bind a compound to the SH2 domain of Src in a Src-expressing cell which includes contacting a compound comprising an amino acid compound to a Src-expressing cell; and binding a compound to the SH2 domain of Src.

Abstract: Disclosed herein are compositions and methods useful for the treatment of cancer, such as breast cancer. In some embodiments, the methods and compositions include human prolactin, or human prolactin in conjunction with a cytotoxic agent. In other embodiments, the methods and compositions include one or more of human prolactin, growth hormone and placental lactogen, or one or more of human prolactin, growth hormone and placental lactogen in conjunction with a cytotoxic agent. In some embodiments, the cytotoxic agent comprises a chemotherapeutic agent.

Abstract: Compositions and methods are provided to destroy internal cancerous lesions selectively by the administration of a combination of a debridement protease enzyme and a denaturant of cell structural proteins and or cell adhesion proteins.

Abstract: Aspects of the invention include compositions and methods for inhibiting the interaction between scaffold proteins and kinases. These compositions and methods find a number of uses including, for example, suppressing tumor growth and metastasis and reducing tumor size and number in a mammal with cancer.