33 results about "Death domain" patented technology

The present invention relates to an immunoliposome preparation having a therapeutic effect on cancer, autoimmune disease, or inflammatory disease. Specifically, the present invention relates to an immunoliposome comprising, as a constituent, an antibody capable of inducing the apoptosis of cells expressing a death domain-containing receptor.

The present invention relates to an immunoliposome preparation or a hydrophobic molecule-modified antibody having a therapeutic effect on cancer, autoimmune disease, or inflammatory disease. Specifically, the present invention relates to an immunoliposome or a hydrophobic molecule-modified antibody comprising, as a constituent, an antibody capable of inducing the apoptosis of cells expressing a death domain-containing receptor.

The present invention relates to compounds which are inhibitors of non-apoptotic regulated cell death, and to pharmaceutical compositions containing such compounds. Furthermore, the present invention relates to the use of such compounds and pharmaceutical compositions in therapy, in particular in the treatment of a condition, disorder or disease that is characterised by non-apoptotic regulated cell-death or where non-apoptotic regulated cell-death is likely to play or plays a substantial role. The compounds and pharmaceutical compositions described herein are also useful in the treatment of a condition, disorder or disease that is characterised by oxidative stress or where oxidative stress is likely to play or plays a substantial role; and / or a condition, disorder or disease that is characterised by activation of (1) one or more components of the necrosome; (2) death domain receptors; and / or (3) Toll-like receptors; and / or (4) players in ferroptotic / ferroptosis signalling, or where activation of any one of (1) to (3) and / or (4) is likely to play or plays a substantial role.

The present invention relates to spiropyrazine compounds which are inhibitors of non-apoptotic regulated cell death, and to pharmaceutical compositions containing such compounds. Furthermore, the present invention relates to the use of such compounds and pharmaceutical compositions in therapy, in particular in the treatment of a condition, disorder or disease that is characterised by non-apoptotic regulated cell-death or where non-apoptotic regulated cell-death is likely to play or plays a substantial role. The compounds and pharmaceutical compositions described herein are also useful in the treatment of a condition, disorder or disease that is characterised by oxidative stress or where oxidative stress is likely to play or plays a substantial role; and / or a condition, disorder or disease that is characterised by activation of (1) one or more components of the necrosome; (2) death domain receptors; and / or (3) Toll-like receptors; and / or (4) players in ferroptotic / ferroptosis signalling, or where activation of any one of (1) to (3) and / or (4) is likely to play or plays a substantial role.

The present invention relates to spiropyrazine compounds which are inhibitors of non-apoptotic regulated cell death, and to pharmaceutical compositions containing such compounds. Furthermore, the present invention relates to the use of such compounds and pharmaceutical compositions in therapy, in particular in the treatment of a condition, disorder or disease that is characterised by non-apoptotic regulated cell-death or where non-apoptotic regulated cell-death is likely to play or plays a substantial role. The compounds and pharmaceutical compositions described herein are also useful in the treatment of a condition, disorder or disease that is characterised by oxidative stress or where oxidative stress is likely to play or plays a substantial role; and / or a condition, disorder or disease that is characterised by activation of (1) one or more components of the necrosome; (2) death domain receptors; and / or (3) Toll-like receptors; and / or (4) players in ferroptotic / ferroptosis signalling, or where activation of any one of (1) to (3) and / or (4) is likely to play or plays a substantial role.

The present invention relates to monospecific or bispecific antibody molecules that specifically bind antigens of Death Receptors, which are members of the tumor necrosis factor (TNF) receptor Superfamily (TNFR-SF) with an intracellular death domain. The invention relates in particular to antibody molecules of the IgG1 isotype having a mutation in the Fc region that enhances clustering of IgG molecules after target binding. The invention further relates to a combination of antibody molecules binding different epitopes on one or more specific Death Receptors. The invention also relates to pharmaceutical compositions containing these molecules and the treatment of cancer using these compositions.

Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription / chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia / mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX / ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

Provided are a method for promoting the lipolysis and fatty acid oxidative metabolism in mammals or cells derived from mammals, a method for downregulating the fat content and the weight of a mammalian body, as well as a method for increasing the intracellular cAMP concentration, increasing the phosphorylation degree and the activity of the hormone-sensitive esterase HSL, enhancing the transcription activity of PPAR alpha and increasing the activities of enzymes involved in a fatty acid beta oxidation process. By simulating the expression of a protein corresponding to a gene responsible for the phosphorylation of the Fas-associated death domain protein, or treating and acting on mammals or cells derived from mammals with a material that can increase the phosphorylation degree of the Fas-associated death domain protein, said methods increases the phosphorylation of the Fas-associated death domain protein.

The invention discloses a micro-molecule polypeptide TAT-p53DM and an application thereof to preparing a medicine for treating or preventing ischemic stroke. A fusion protein polypeptide TAT-p53DM of a TAT protein transduction domain and p53DM is artificially synthesized; TAT carries p53DM protein polypeptide to pass through a blood brain barrier through blood so as to be taken by nerve cells; used in an in-vitro and in-vivo ischemic stroke model, the micro-molecule polypeptide TAT-p53DM is capable of effectively playing a biological role in blocking binding between death domain of death associated protein kinase 1 (DAPK1DD) and tumor suppression protein p53DNA binding motifs (p53DM), inhibiting signals capable of causing neuronal apoptosis and necrosis at DAPK1 downstream, and reducing ischemic stroke brain injury; moreover, molecular targets are provided for further developing medicines for clinically treating ischemic stroke.

The present invention relates to an antibody which has a therapeutic effect on cancer, autoimmune diseases or inflammatory diseases. Namely, the present invention relates to an antibody which exhibits an apoptosis-mediated cytotoxic activity on a cell expressing a death domain-containing receptor. The present invention addresses the problem of providing a drug which has a therapeutic effect on cancer. The present invention clarifies that a novel anti-DR5 antibody, which is capable of inducing apoptosis in a cell, has a remarkable cytotoxic activity compared with the conventional anti-DR5 antibodies.

Methods and compositions for treating inflammatory bowel disease by promoting mucosal healing in the gastrointestinal (GI) tract are encompassed herein. More particularly, methods and compositions described herein relate to agents that activate mononuclear phagocytes (MNPs) in the GI tract and, in turn, regulate the activity of interleukin (IL)-22-producing group 3 innate lymphoid cells (ILC3) in close proximity thereto.

Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription / chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia / mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX / ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

The present invention belongs to the pharmaceutical field. The present invention particularly relates to the medicine of pentamidine combined with the legend of the death structure receptor in treating the tumor and the leukemia. The ligand of the death structure receptor in the present invention comprises TRAIL, TNF-alpha or the analogues, which is the combination of the pentamidine with the metabolite or the analogues. The benefit of the present invention is that the pentamidine sensibility of the leukemia cell of the ligand of the death structure receptor. In the clinical field, when thepentamidine of the therapeutic drug concentration is applied in the leukemia cell, which is tolerant to the ligand of the death structure receptor, the apoptosis can be induced; therefore the purposefor the leukemia treatment is realized.

Disclosed herein is the discovery that administration of the NRIF3 family of transcriptional coregulators (NRIF3 and related molecules) to breast cancer cells induce rapid and profound apoptosis (nearly 100% cell death within 24 h). A novel death domain (DD1) was mapped to a short 30 amino acid region common to all members of the NRIF3 family. Two other death domains (DD2 and DD3) were also found to have effective breast cancer killing activities. Mechanistic studies showed that DD1-induced apoptosis occurred through a novel caspase-2 mediated pathway that involved mitochondria membrane permeabilization but did not require other caspases. Interestingly, cytotoxicity of NRIF3 related molecules was cell-type specific, as they selectively killed breast cancer or related cells but not other examined cells of different origins, suggesting the presence in breast cancer cells of a specific death switch that can be selectively triggered by NRIF3 and related molecules. Also disclosed are strategies utilizing NRIF3 related molecules and / or targeting this death switch for the development of novel and more selective therapeutics against breast cancer.

Novel TNF receptor death domain (“TNF-R1-DD”) ligand proteins are disclosed. Polynucleotides encoding the TNF-R1-DD ligand protein are also disclosed, along with vectors, host cells, and methods of making the TNF-R1-DD ligand protein. Pharmaceutical compositions containing the TNF-R1-DD ligand protein, methods of treating inflammatory conditions, and methods of inhibiting TNF-R death domain binding are also disclosed. Methods of identifying inhibitors of TNF-R death domain binding and inhibitors identified by such methods are also disclosed.