83 results about "Inhibitor of apoptosis" patented technology

IAP binding molecules and compositions including these are disclosed. The IAP binding molecules interact with IAPs (inhibitor of apoptosis proteins) in cells and may be used to modify apoptosis in cells treated with such molecules. Embodiments of these compounds have a K_d of less that 0.1 micromolar. Methods of using these IAP binding molecules for therapeutic, diagnostic, and assay purposes are also disclosed.

Peptides and peptidomimetics capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins) are disclosed. The peptides and mimetics are based on the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptides and peptidomimetics for therapeutic purposes and for rational drug design.

Novel compounds that inhibit the binding of the Smac protein to Inhibitor of Apoptosis Proteins (IAPs) of the formula I

T cell immune responses are enhanced by presentation of antigen to CD8⁺ T cells using a chimeric nucleic acid immunogen or vaccine that links DNA encoding an antigen with DNA encoding a polypeptide that targets or translocates the antigenic polypeptide to which it is fused (immunogenicity-potentiating polypeptides or “IPP”). By inhibiting apoptosis in the vicinity of a T cell responses to such a nucleic acid immunogen, even more potent immune responses are attained. The present strategy prolongs the survival of DNA-transduced cells, including dendritic cells (DCs), thereby enhancing the priming of antigen-specific T cells and increase potency. Co-delivery of DNA encoding an inhibitor of apoptosis, including (a) BCL-xL, (b) BCL-2, (c) XIAP, (d) dominant negative caspase-9, or (e) dominant negative caspase-8, or (f) serine protease inhibitor 6 (SPI-6) which inhibits granzyme B, with DNA encoding an antigen, prolongs the survival of transduced DCs and results in significant enhancement of antigenspecific T cell immune responses that provide potent antitumor effects. Thus, co-administration of a DNA vaccine encoding antigen linked to an IPP along with one or more DNA constructs encoding an anti-apoptotic protein provides a novel way to enhance vaccine potency.

The invention provides methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain associated with a neurodegenerative diseases that is characterized by an excess buildup of buildup of intracellular protein aggregates. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding an inhibitor of apoptosis protein (IAP) to cells in the region.

Activated protein C (APC), prodrug, and/or a variant thereof may be used as an inhibitor of apoptosis or cell death and/or a cell survival factor, especially for stressed or injured cells or tissues of the nervous system including subjects with neurode-generative disorders. Novel biological functions (e.g., neuroprotection) can be independent or separated from inhibition of clotting or inflammation, and other biological properties of APC (e.g., antithrombotic activity, ability to reduce NFκB-regulated gene expression). It can be used in the treatment of disease or other pathological conditions by at least inhibiting the p53-dependent and/or caspase-3-dependent pro-apoptotic signaling pathways in stressed or injured cells. Thus, APC, prodrugs, and variants thereof (e.g., APC protease domain mutants with reduced anti-coagulant activity) are prototypes of a class of agents for preventing apoptosis or cell death and/or promoting cell survival by direct action on brain cells. New protein C and/or APC variants with reduced anticoagulant activity may be selected thereby.

The present invention provides compounds that can protect mammalian cells from the damaging effects of chemotherapy, irradiation, or in other situations in which it is desirable to protect tissue from the consequences of clinical or environmental stress.

This invention provides caspase inhibitors of formula I:

wherein Z is oxygen or sulfur; R¹is hydrogen, —CHN₂, R, CH₂OR, CH₂SR, or —CH₂Y; Y is an electronegative leaving group; R² is CO₂H, CH₂CO₂H, or esters, amides or isosteres thereof; R³ is a group capable of fitting into the S2 subsite of a caspase enzyme; R⁴ and R⁵ are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

A pharmaceutical composition including, as an active ingredient, one of the following proteins (I) and (II): (I) an apoptosis inhibitor of macrophage; and (II) a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of the apoptosis inhibitor of macrophage and having homology to the amino acid sequence of the apoptosis inhibitor of macrophage, and has a function of inhibiting the differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes.

The invention provides a method for preventing and treating bemisa babaci by utilizing an RNA (Ribose Nucleic Acid) interference (RNAi) technology, belonging to the technical field of agriculture and biology. The method provided by the invention comprises the following steps of: (1) selecting a target sequence IAP (Inhibitor Of Apoptosis Protein) gene of RNAi according to a gene sequence of the bemisa babaci and designing a PCR (Polymerase Chain Reaction) amplification primer of the target sequence; (2) extracting the RNA of the bemisa babaci and carrying out transcription to obtain a cDNA (Complementary Deoxyribonucleic Acid); then carrying out PCR amplification on the cDNA and purifying to prepare a target gene; (3) inserting the target gene into an expression vector to prepare the expression vector containing the target gene; (4) and transforming the expression vector containing the target gene into a crop to obtain a transgenic crop for preventing and treating bemisa babaci; and planting the crop. The method provided by the invention has important guiding value and theoretical significance on researching the gene function of the bemisa babaci by utilizing the RNAi technology, preventing and treating the bemisa babaci by utilizing the RNAi technology, and preventing and treating the bemisa babaci by utilizing the transgenic crop.

Assays are disclosed for identifying peptides and peptidomimetics for promoting apotosis in cells, through a pathway involving the Inhibitor of Apoptosis Proteins (IAPs), exemplified by XIAP, and the mitochondrial protein Smac/DIABOLO (hereinafter Smac) and homologs thereof. Also disclosed are IAP-binding peptides and peptidomimetics identified through the use of the assay.

The invention belongs to the technical field of molecular biological detection, and provides a method for detecting and identifying six pairs of PCR (polymerase chain reaction) primers of six kinds of Listeria bacteria from an environment respectively. The PCR primer pairs are designed according to a specific target gene iap (inhibitor of apoptosis protein) of the Listeria bacteria, the target gene is high in stability and specificity, and the six kinds of Listeria bacteria existing in the environment can be rapidly and accurately identified by virtue of a reasonable PCR system and a gel electrophoresis detection means. The detection method comprises the following steps of (1) extracting a sample DNA (deoxyribonucleic acid), and performing PCR amplification by adopting different primer pairs respectively; (2) judging whether a sample to be detected contains the Listeria bacteria or not according to the length of a PCR amplification product fragment. According to the method, the six kinds of Listeria bacteria in the environment and a food sample can be rapidly, accurately and sensitively detected and identified, so that the efficiency is improved, time is saved, and moreover, the detection cost is lowered.

Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).

A method and compound for enhancing the lethality of an anti-cancer therapy, such as radiation, chemotherapy, or TRAIL protein, are disclosed. The compound is composed of morpholino subunits joined by phosphorodiamidate linkages, and has a targeting sequence that is complementary to an AUG start, IRES, or splice-donor region of the transcript for human X-linked inhibitor of apoptosis protein (XIAP). The method includes exposing cancer cells to the compound.

A DNA vaccine suitable for eliciting an immune response against cancer cells comprises a DNA construct operably encoding a cancer-associated Inhibitor of Apoptosis-family protein and an immunoactive gene product, such as a cytokine or a ligand for a natural killer cell surface receptor, in a pharmaceutically acceptable carrier. A preferred cytokine is CCL21. Preferred ligands for a natural killer cell surface receptor include human MICA, human MICB, human ULBP1, human ULBP2, and human ULBP3. The cancer-associated Inhibitor of Apoptosis (IAP)-family protein is preferably a survivin protein or livin protein. Method of inhibiting tumor growth by administering the vaccine of the invention to a mammal is also described.

Provided are methods for promoting axon regeneration of a Central Nervous System (CNS) neuron and promoting nerve function following injury to a CNS neuron, for example, brain and/or spinal cord injury. Axon regeneration in a CNS neuron or nerve function following injury to a CNS neuron can be promoted by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject suffering from a CNS disorder, wherein a symptom of the CNS disorder is axon degeneration.

The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an alpha4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.