32 results about "Apoptosis signaling" patented technology

A novel nucleic acid construct for down-regulating angiogenesis in a tissue of a subject is provided. The nucleic acid construct includes: (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain fused to an effector domain of an apoptosis signaling molecule; and (b) a second polynucleotide region encoding a cis acting regulatory element being for directing expression of the chimeric polypeptide in a specific tissue or cell; wherein the ligand binding domain is selected such that it is capable of binding a ligand present in the specific tissue or cell, whereas binding of the ligand to the ligand binding domain activates the effector domain of the apoptosis signaling molecule. Also provided are methods of utilizing this nucleic acid construct for treating diseases characterized by excessive or aberrant neo-vascularization or cell growth.

Compositions and methods for restoring killing of cancer cells are provided. Preferably, the compositions are administered to a subject in an effective amount to antagonize, inhibit, reduce, or block B7-H1 mediated signal transduction in cancer cells expressing B7-H1. It has been discovered that B7-H1 transmits an anti-apoptotic signal in cancer cells that increases the resistance of the cancer cells to CTL mediated cytolysis and to Fas induced cell death. It is believed that blocking the transmission of the anti-apoptotic signal by B7-H1 increases the susceptibility of the cancer cells to apoptosis and CTL cytolysis thereby enhancing the death of cancer cells. Preferred compounds or B7-H1 antagonists include antibodies that bind to B7-H1, B7-H1 receptors, or ligands of B7-H1 such as PD-I or B7-1. Additional B7-H1 antagonists include small molecules, for example small molecules that bind the cytoplasmic portion of B7-H1 or the extracellular portion of B7-H1 and inhibit, reduce, block or interfere with B7-H1 signal transduction. Methods for treating one or more symptoms associated with cancer or hyperproliferation are also provided.

The invention provides a method for knocking out a KDM2A gene of HEK293T cells with a CRISPR-CAS9 technology. The method comprises the steps as follows: (1), cell transfection; (2), cell genome extraction; (3), PCR identification; (4), gene level verification; (5), protein level verification: whether K3, K7-1 and K7-2 are KDM2A gene-deficient is further verified by Western blotting after a mutantcell line is verified at the gene level. The invention further provides a KDM2A knockout HEK293T cell line prepared with method and an application of the KDM2A knockout HEK293T cell line as a cell model in study of cell proliferation and apoptosis signaling pathways involved in KDM2A methylase.

A novel nucleic acid construct for down-regulating angiogenesis in a tissue of a subject is provided. The nucleic acid construct includes: (a) a first polynucleotide region encoding a chimeric polypeptide including a ligand binding domain fused to an effector domain of an apoptosis signaling molecule; and (b) a second polynucleotide region encoding a cis acting regulatory element being for directing expression of the chimeric polypeptide in a specific tissue or cell; wherein the ligand binding domain is selected such that it is capable of binding a ligand present in the specific tissue or cell, whereas binding of the ligand to the ligand binding domain activates the effector domain of the apoptosis signaling molecule. Also provided are methods of utilizing this nucleic acid construct for treating diseases characterized by excessive or aberrant neo-vascularization or cell growth.

The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) inhibiting compounds of the formulawherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, ester, stereoisomer, tautomer, solvate, hydrate, or combination thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, ester, stereoisomer, tautomer, solvate, hydrate, or combination thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The invention generally relates to compositions and methods for identifying Apoptosis signaling pathway inhibitors and activators.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, ester, stereoisomer, tautomer, solvate, hydrate, or combination thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I),and pharmaceutically acceptable salts thereof, which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The invention discloses a rhodamine dye containing a water-soluble substituent and a functional derivative (a zinc ion probe and an antibody labeled dye) of the rhodamine dye. The rhodamine dye has a structure as shown in a general formula I. After the N-site of a parent nucleus of the dye is connected with different water-soluble substituents, the biocompatibility of the parent nucleus of the dye is greatly improved; and specifically, non-specific staining in cells is remarkably reduced, cell apoptosis signals do not appear any more, phototoxicity is remarkably reduced (the zinc ion probe), labeling efficiency is improved, observation time is prolonged (the antibody labeled dye) and the like. The fluorescent dye disclosed by the invention can be applied to the fields of observing insulin release of in-vitro live pancreas islets, immunofluorescence labeling and the like.

The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) . inhibiting compounds of the formulawherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds, to methods and intermediates useful for making the compounds, and to methods of using the compounds.

The invention relates to a donor of hydrogen sulfide and its preparation method and application, belonging to the technical field of medicine. The donor of hydrogen sulfide provided by the present invention has a chemical name of S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-L-cysteine ​​methyl ester, The chemical structural formula is shown in formula (I); the hydrogen sulfide donor (MTC) provided by the present invention can effectively treat the disease of ischemic stroke by activating the PI3K / AKT pathway, inhibiting the mitochondrial apoptosis signaling pathway, and reducing the internal To achieve the purpose of effective treatment of ischemic stroke, there are various therapeutic targets such as cytoplasmic reticulum stress, activation of ERK-MEK signaling pathway, increase of survival rate of nerve cells or protection of neurons from ischemic injury.

The present invention discloses a device and a kit adapted for selection of cells that are resistant to receptor-mediated apoptosis and a method for using the device and kit. The device enables negative selection of mature immune cells which induce graft versus host disease (GvHD) out of a heterogeneous cell population which is introduced into the device. The device enables an efficient cell selection in simplified and cheaper setting by an off the shelf product—a solution that currently do not exist. The present invention further discloses uses for the device.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which is associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

The invention discloses an apoptosis signal regulating kinase inhibitor and an application thereof. The apoptosis signal regulating kinase inhibitor is a compound represented by general formula I, anda tautomer or a pharmaceutically acceptable salt thereof. The apoptosis signal regulating kinase inhibitor is a compound with a novel structure. Pharmacodynamic experiments prove that the compound has good inhibition capability on an ASK1 receptor, can be used for effectively inhibiting fibrosis in vitro and has low toxicity on normal cells. Therefore, the compound provided by the invention can be used for treating various fibrosis and related diseases.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The present invention discloses compounds of Formula (I),and pharmaceutically acceptable salts thereof, which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).

The invention provides a method for knocking out a KDM2A gene of HEK293T cells with a CRISPR-CAS9 technology. The method comprises the steps as follows: (1), cell transfection; (2), cell genome extraction; (3), PCR identification; (4), gene level verification; (5), protein level verification: whether K3, K7-1 and K7-2 are KDM2A gene-deficient is further verified by Western blotting after a mutantcell line is verified at the gene level. The invention further provides a KDM2A knockout HEK293T cell line prepared with method and an application of the KDM2A knockout HEK293T cell line as a cell model in study of cell proliferation and apoptosis signaling pathways involved in KDM2A methylase.

The invention discloses a cell apoptosis signal regulating kinase inhibitor and application thereof. Compounds as shown in general formula I, tautomers thereof or pharmaceutically acceptable salts thereof: the present invention provides a class of compounds with novel structures, and pharmacodynamic experiments prove that the compounds of the present invention have a relatively high effect on ASK1 receptors. Good inhibitory ability, can effectively inhibit the formation of fibrosis in vitro, and has low toxicity to normal cells. Accordingly, the compounds of the present invention are useful in the treatment of a variety of fibrosis and related diseases.

The present invention discloses a device and a kit adapted for selection of cells that are resistant to receptor-mediated apoptosis and a method for using the device and kit. The device enables negative selection of mature immune cells which induce graft versus host disease (GvHD) out of a heterogeneous cell population which is introduced into the device. The device enables an efficient cell selection in simplified and cheaper setting by an off the shelf product—a solution that currently do not exist. The present invention further discloses uses for the device.