Abstract: A Smac mimetic therapy wherein the Smac mimetic is selected and developed based at least in part on its cIAP degradation properties.

Abstract: The invention provide isolated peptides, protides and conjugates having novel peptide sequences which are able to induce antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. The invention also provides a method of inducing programmed cell death in a cell by contacting the cell with an isolated peptide, protide or conjugate described herein. In some aspects, the method can be used in the diagnosis, prevention, or treatment of a disease, such as an infection, cancer, autoimmune disease, or inflammatory disease.

Abstract: The present invention describes compounds of the formula pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them, and their use in therapy.

Abstract: Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: wherein R1,R2,R3,R4,R5 and R6 are as described herein.

Abstract: The disclosure provides Apo-2 ligand variant polypeptides. Methods of making and chemically modifying Apo-2 ligand variant polypeptides are also provided. In addition, formulations of Apo-2 ligand variant polypeptides are provided. In addition, therapeutic methods for using Apo-2 ligand variant polypeptides are provided.

Abstract: Novel agents are described that bind to Eph receptors. Methods of using these agents to modulate the activity of Eph receptors, stimulate apoptosis, and deliver therapeutic agents are also described. Methods of screening for agents capable of selectively binding to Eph receptors are also described.

Abstract: Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic. acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.

Abstract: A method of inhibiting apoptosis in a cell includes administering to a cell an effective amount of a cell penetrating peptide (CPP), wherein the CPP consists of about 5 to about 41 amino acids and is substantially homologous to a portion of the C-terminal region of IFN?R2.

Abstract: Provided are methods and compositions for maintaining the viability of photoreceptor cells and/or retinal pigment epithelial cells in a subject with an ocular disorder including, for example, age-related macular degeneration (AMD) (e.g., dry or neovascular AMD), retinitis pigmentosa (RP), or a retinal detachment. The viability of the photoreceptor cells and/or the retinal pigment epithelial cells can be preserved by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject having an eye with the ocular condition. The compositions, when administered, maintain the viability of the cells, thereby minimizing the loss of vision or visual function associated with the ocular disorder.

Abstract: Disclosed are SPARC and albumin binding peptides for the targeting of disease sites, such as tumors, with therapeutic and diagnostic agents In particular, compositions comprising SPARC binding peptide—Antibody Fc domain fusion proteins and methods of their use are disclosed.

Abstract: The present invention provides compounds of formula M-L-M? (where M and M? are each independently a monomeric moiety of Formula (I) and L is a linker). The dimeric compounds have been found to be effective in promoting apoptosis in rapidly dividing cells.

Abstract: A purified polypeptide for inhibiting binding of BCL-2 to IP3 receptors includes an amino acid sequence consisting of about 10 to 80 amino acids. The amino acid sequence has a sequence identity at least 90% homologous to a portion of SEQ ID NO:1. The polypeptide inhibits binding of Bcl-2 to IP3 receptors of cells that express IP3R and Bcl-2 and induces apoptosis in a cell.

Abstract: The present invention provides methods to prevent photoreceptor death. In particular, the present invention provides peptides which prevent FAS-mediated photoreceptor apoptosis.

Abstract: The present invention relates generally to variants and peptides of the mitochondrial protein, voltage-dependent anion channel (VDAC) and to polynucleotides encoding same. In particular, the present invention is directed to N-terminal truncated and mutated VDAC and specific amino acid and polynucleotide sequences thereof useful in inhibiting apoptosis, and to pharmaceutical compositions comprising same useful in the treatment of diseases associated with excess apoptosis.

Abstract: The present invention aims to provide a method for the prophylaxis or treatment of metabolic syndrome, which can discontinue the domino effect-like chain of diseases in metabolic syndrome in the upstream by suppressing infiltration of macrophage into the adipose tissues. The present invention provides a method for the prophylaxis or treatment of a metabolic syndrome, including a step of administering an AIM inhibitor to a subject.

Abstract: The invention provides compositions comprising one or more isolated factors from a microenvironment of human embryonic stem cells (hESCs), including, but not limited to, Lefty and inhibitors of Nodal. The invention also provides methods of utilizing factors derived from human embryonic stem cells (hESC) and their microenvironment to treat and prevent tumor formation and progression and to inhibit tumor cell aggressiveness. The invention further provides methods of inhibiting tumor cell growth and/or treating aggressive tumors in a mammal comprising administering to the mammal, having at least one tumor cell present in its body, an effective amount of an inhibitor of Nodal activity.

Abstract: The present invention is directed to a multimeric agent and a multimeric conjugate formed from this multimeric agent and a biologically active agent. Said multimeric conjugates have a longer life time in vivo and an increased avidity compared to the unmodified biologically agent. The present invention is further directed to a pharmaceutical or diagnostic composition containing said conjugate as well as to a method of its production. The invention additionally provides the use of said conjugates for the detection, determination, separation and/or isolation of a specific binding partner and for the diagnosis, prophylaxis and treatment of diseases in which the specific binding partner is directly or indirectly involved.

Abstract: The present invention is a composition composed of a therapeutic agent encapsulated in a copolymer of an N-alkylacrylamide, a vinyl monomer, and a polyethylene glycol (PEG) conjugate and a method for using the same in the treatment or prevention of a disease or condition.

Abstract: This invention relates to anti-cancer compounds and to methods for treating or preventing cancer. In particular, the invention concerns pro-oxidant anti-cancer compounds, such as pro-oxidant forms of vitamin E that selectively interact with complex II of the mitochondrial respiratory chain of cancerous cells, generate reactive oxygen species and induce apoptosis of those cells.

Abstract: The present invention is related with the field of the medicine, particularly with the use of an APL peptide or its analogues derived from the human heat shock protein of 60 kDa, for the manufacture of a pharmaceutical composition for the treatment of Crohn's disease, ulcerative colitis and diabetes mellitus type 1. This peptide is biodistributed into the gastrointestinal tract and also promotes the induction of apoptosis in activated intestinal lamina propria and peripheral blood T cells of patients with Crohn's disease. Furthermore, this peptide induces apoptosis in mononuclear cells of patients with diabetes mellitus type 1.

Abstract: Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: Disclosed is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I or II or a salt thereof, in which R1, R2, R3, R100, R200, R300, A, A1, BG, Q and Q1 are substituents described herein. Also disclosed is the use of compounds of Formula I and II to treat proliferative disorders such as cancer.

Abstract: In one aspect the present invention provides methods for inhibiting cell death or inflammation in a mammal, wherein the methods each include the step of administering to a mammal a Bcl protein in an amount sufficient to inhibit cell death or inflammation in the mammal. The invention also provides methods for identifying a Bcl protein that inhibits cell death or inflammation when administered to a mammal.

Abstract: The present invention provides compositions and methods to prevent apoptosis. In particular, provided herein are compositions and methods which prevent FAS-mediated photoreceptor apoptosis.

Abstract: A method for treatment of disease classified as any of grade 1 to 3 according to the ICRS classification of osteoarthritis, any of grade 1 to 3 according to the Kellgren-Lawrence classification of osteoarthritis, or any of grade 1 to 3 according to the Outerbridge classification of osteoarthritis, the method includes a step of administrating an agent containing an anti-Fas IgM antibody as an active ingredient.

Abstract: A compound of Formula 1: (I) or salt thereof, as well as methods of making compounds of Formula 1, methods of using compounds of Formula 1 to treat proliferative disorders such as cancer, and related compounds, composition, and methods.

Abstract: The present invention encompasses methods and compositions for treating an ocular disease, disorder or condition in a mammal. The invention includes a population of mesenchymal stromal cells that possess anti-inflammatory, anti-apoptotic, immune modulatory and anti-tumorigenic properties. The invention includes administration of TSG-6, STC-1, or a combination thereof to the ocular as a treatment for an ocular disease, disorder or condition in a mammal.

Abstract: Disclosed is a method of enhancing the response of cancer cells in a mammal to treatment with a death receptor ligand, which method comprises contacting the cancer cells with a death receptor ligand in conjunction with an effective amount of a compound described herein, for example, a cucurbitacin (I) or a withanolide (II). Also disclosed is a method of inducing apoptosis in cancer cells in a mammal, comprising contacting the cancer cells with a compound described herein, for example, a cucurbitacin (I) or a withanolide (II) and also contacting the cancer cells with a death receptor ligand, whereby apoptosis is induced in the cancer cells.

Abstract: The invention relates to a method for transiently immortalizing cells according to which immortalization proteins are introduced into the cells from outside. The invention also relates to a method for producing cells according to which organ-related cells are transiently immortalized by the exogenous supply of immortalization proteins and are remortalized after their expansion. The invention further relates to the cells produced according to the inventive method, to the use of said cells for producing a transplant and to the immortalization proteins used in the method.

Abstract: Described herein are methods and compositions related to the discovery that the Follistatin-like 1 protein (Fstl-1) has metabolic and cardioprotective effects in vivo. Fstl-1 and portions and derivatives or variants thereof can be used to treat or prevent metabolic diseases or disorders and to treat or prevent cardiac damage caused by interrupted cardiac muscle blood supply.

Abstract: The invention relates to delocalization molecules, methods for the production thereof, and the use thereof as medicaments, especially for treating tumors.

Abstract: The present invention includes methods of making and methods of using peptidomimetics compositions that mimic ?-helical BH3 sequences in cells. The peptidomimetics can be used to mimic ?-helical BH3 sequences and kill cancer cells.

Abstract: The present invention relates to novel Death Domain Containing Receptor-4 (DR4) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR4 proteins. DR4 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR4 activity and methods for using DR4 polynucleotides and polypeptides. The invention also relates to the treatment of diseases associated with reduced or increased levels of apoptosis using antibodies specific for DR4, which may be agonists and/or antagonists of DR4 activity.

Abstract: The present invention relates a novel cell-killing peptide, particularly to a cell-killing peptide that exploits a specific region at the C-terminus of Noxa protein, a “BH3-only” member of Bcl-2 family causing apoptosis and fusion proteins containing the same. According to the present invention, the cell-killing peptide (CKP) effectively kills a cancer cell such as HeLa or HCT116 when it is conjugated with PTD or CTD domain. Therefore, the cell-killing peptide of the present invention is still stronger to kill cells, compared with conventional substances such as TRAIL, and will be applied widely for various cell therapies, especially in cancer treatment.

Abstract: Fusion proteins which act on the TWEAK and TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, as well as other diseases such as alloimmune diseases and cancer.

Abstract: The present invention provides fusion proteins comprising an extracellular domain of a VEGF receptor and a death ligand. The fusion proteins bind to VEGF and to death receptors on tumor cells thereby inhibiting VEGF activation of VEGF receptors and inducing apoptosis in the tumor cells. Fusion proteins of the present invention are useful for inducing apoptosis and cytotoxic effects in cells, treating cancer and diseases or disorders related to unregulated angiogenesis and/or vasculogenesis. Thus, this invention further provides methods for treating angiogenesis related diseases using the fusion proteins, polynucleotides encoding the fusion proteins, vectors containing the polynucleotides, pharmaceutical compositions and kits containing the fusion proteins or the polynucleotides encoding the fusion proteins.

Abstract: A method of inhibiting apoptosis in a cell includes administering to a cell an effective amount of a cell penetrating peptide (CPP), wherein the CPP consists of about 5 to about 41 amino acids and is substantially homologous to a portion of the C-terminal region of IFN?R2.

Abstract: The invention relates to caspases and to extracellular use of caspases for regulating cell functions.

Abstract: A compound, or a pharmaceutically acceptable salt or ester thereof, of formula I: X—W wherein X is a caspase-selective structure and W has the structure of —NH—CH(Y)(Z) wherein Y is a structure that can form a reversible covalent bond with a caspase; and Z is selected from a carboxyl moiety or a carboxylic acid mimetic.

Abstract: Described herein is the discovery that human interleukin-1? convertase (ICE) is structurally similar to the protein encoded by the C. elegans cell death gene, ced-3. Comparative and mutational analyses of the two proteins, together with previous observations, suggest that the Ced-3 protein may be a cysteine protease like ICE and that ICE may be a human equivalent of the nematode cell death gene. Another mammalian protein, the murine NEDD-2 protein, was also found to be similar to Ced-3. The NEDD-2 gene is implicated in the development of the murine central nervous system. On the basis of these findings, novel drugs for enhancing or inhibiting the activity of ICE, ced-3, or related genes are provided. Such drugs may be useful for treating inflammatory diseases and/or diseases characterized by cell deaths, as well as cancers, autoimmune disorders, infections, and hair growth and hair loss. Furthermore, such drugs may be useful for controlling pests, parasites and genetically engineered organisms.

Abstract: The present invention demonstrates that P2X7 receptor induced apoptosis may be specific for cancerous cells. Treatment with the P2X7 ligand BzATP, increased cellular apoptosis with no associated inflammatory changes or abnormal skin or systemic effects. In mice treated with DMBA/TPA, BzATP decreased papilloma skin formation. BzATP also induced involution of developed papillomas and stimulated apoptosis in keratinocytes outgrowing at the base of developed papillomas. These data show that (a) P2X7 regulates apoptosis of epidermal cells; (b) in vivo, local administration of a drug that activates the P2X7 receptor can inhibit development and progression of epidermal premalignant lesions.

Abstract: The present invention relates to inhibitors of MALT1 proteolytic and/or autoproteolytic activity. More specifically, it relates to compounds such as, but not limited to peptide derivates such as Z-LSSR-CHO (see SEQ ID NO:1), Z-LSSR-CMK (see SEQ ID NO:1), Z-GASR-CHO (see SEQ ID NO:2), and Z-GASR-CMK (see SEQ ID NO:2), and small compounds such as 5-{[5-(3-chloro-4-methylphenyl)-2-furyl]methylene}-2-thioxodihydro-4,6(1H,5H)-pyrimidinedione and variants thereof, and the use of those compounds for the preparation of a medicament. The invention relates further to a method to screen for inhibitors of the MALT1 proteolytic and/or autoproteolytic activity.

Abstract: The present invention relates to novel ficolin-associated polypeptides, and polypeptides derived from these ficolin-associated polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases, as well as the use as biomarkers. The present invention further relates to anti-bodies recognising such novel ficolin-associated polypeptides, and polypeptides derived thereof, nucleic acid molecules encoding such polypeptides, vectors and host cells used in the production of the polypeptides.

Abstract: A method of treatment for preventing or reducing tumor growth in liver of a patient includes administering to the patient an effective about of taurolidine, taurultam or a mixture thereof, so as to prevent or reduce the tumor growth in the patient.

Abstract: The invention relates to diazo bicyclic Smac mimetics that are tethered through a covalent linker to give a bivalent species. Bivalent diazo bicyclic Smac mimetics function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs). The invention also relates to the use of bivalent diazo bicyclic Smac mimetics for inducing or sensitizing cells to the induction of apoptotic cell death. Thus, compounds of the invention are useful in the treatment, amelioration, or prevention of hyperproliferative diseases such as cancer.

Abstract: The present invention provides ZPA polypeptides, antibodies, nucleic acid molecules, antagonists, agonists, potentiators and compositions relating to ZPA polypeptides, and methods of identifying, making and using the same, that are useful for treating and preventing diseases and for medical diagnosis and research. The present invention also provides model systems for the intrinsic apoptotic pathway.

Abstract: The use of flagellin and flagellin related polypectides for the protection of mammals from the effects of apoptsis is described.

Abstract: The present invention is related to a method for inducing the cancer cell apoptosis or inhibiting the cancer cell migration by inhibiting the expression of ribose-5-phosphate isomerase A.

Abstract: This invention relates to compositions and methods for modulating apoptosis by regulating the activity of endoplasmic reticulum transmembrane glucose regulated protein 78 (GRP78).

Abstract: Cell-permeable caPCNA-derived peptides and their variants serve as therapeutic compositions to reduce the proliferation of cancerous cells and also augment cytotoxic effects of chemotherapeutics.