26 results about "Caspase inhibitors" patented technology

One aspect of the present invention relates to a pharmaceutical composition for preventing or treating angiogenesis-related ocular diseases, comprising a caspase inhibitor or pharmaceutically acceptable salts thereof. The pharmaceutical composition has an excellent effect of inhibiting apoptosis and inflammatory activity, and exhibits an angiogenesis-inhibitory effect, and thus can be used for the prevention or treatment of angiogenesis-related ocular diseases.

This disclosure relates to wound treatment. It discloses compositions and methods for treating wounds, particularly chronic wounds, using caspase-3 inhibitors. It also discloses methods for detecting wounds based on the level of cleaved caspase-3 and / or caspase-3 activity in wound samples.

The present invention relates to an injectable formulation comprising, as an active pharmaceutical ingredient (API), an isoxazoline derivative useful as a caspase inhibitor, or a pharma- ceutical acceptable salt thereof. The injectable formulation according to the present invention comprises a first agent comprising a high-capacity API and a second agent which is a solvent capable of dissolving the first agent. The first agent and the second agent can be mixed together immediately before administration to prepare the formulation. Since the formulation contains the active API stably, it has an advantage that it can be expected to have an effective medicinal effect when administered to a patient.

Up-regulation of caspase has been found in COVID-19 patients, and also occurs in patients suffering from diabetes, hypertension, metabolic syndrome, and other conditions. Such up-regulation can be responsible for poor clinical outcomes in patients having such diseases or disorders, as such up-regulation leads to a process called pyroptosis: death and malfunction of immune system cells, particularly of certain types of lymphocytes. An inhibitor of caspase such as a caspase 1 inhibitor, or “pan-caspase” inhibitor (i.e., an inhibitor of multiple caspase types including caspase-1), can be used to treat COVID-19 patients or individuals at risk of infection, by limiting the malfunction of the immune system. A caspase-1 or pan-caspase inhibitor is advantageously administered before or very early in the course of infection by a positive-sense, single-stranded RNA virus such as SARS-CoV, MERS-CoV, or SARS-Cov-2.

The present disclosure relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Ring A, G1, RC, X, RD1, RD2, and RD3 are as described herein, methods of preparation and intermediates useful in said preparation, methods of treatment and prevention (e.g., of Caspase-4 mediated diseases and disorders), and pharmaceutical compositions comprising same. Compounds of Formula (I), and pharmaceutically acceptable salts thereof, are designed as selective Caspase-4 allosteric inhibitors, sparing Caspase-1, and have also been found to be selective against Caspase-5 and are thus, in embodiments, considered dual Caspase-4 / 5- inhibitors. The present disclosure further relates to the Applicant's discovery of a new and allosteric human Caspase-4 binding pocket, and methods of binding to (and compounds inhibiting the activity of) same, methods of treatment and prevention, and pharmaceutical compositions comprising such compounds.

A lipid nanoparticle (liposome) comprising: (i) an outer shell comprising a lipid formulation; and (ii) one or more therapeutic agents which prevent apoptosis of a target cell is provided. The therape

The present invention relates to a cell lysate wherein the lysis buffer comprises magnesium acetate, the phosphorylation inhibitor K3L, the agonist of dephosphorylation GADD34 and a caspase inhibitor for use in, or as, a cell-free system and a method for preparing a cell-free protein synthesis system. Further provided is a method for expressing a protein in the cell-free protein synthesis system, a method for screening for a candidate compound for an effect on a target molecule and a use of the cell-free protein synthesis system. The present invention also provides a kit for the above-mentioned cell-free systems.

One aspect of the present invention relates to a pharmaceutical composition for preventing or treating heart diseases, the composition comprising a caspase inhibitor or a pharmaceutically acceptable salt thereof. The pharmaceutical composition has an excellent effect of inhibiting apoptosis and inflammatory activity, and thus can be used for preventing or treating heart diseases, such as cardiac hypertrophy, caused by atrial fibrillation, heart failure, or hypertension.

The present invention relates to an injectable formulation comprising, as an active pharmaceutical ingredient (API), an isoxazoline derivative or a pharma- ceutically acceptable salt thereof, which is useful as a caspase inhibitor. The injectable formulation according to the present invention comprises a first agent comprising a high-dose API and a second agent comprising a reconstitution solution, and can be prepared by mixing the first agent and the second agent just before administration to a patient. Since the injectable formulation stably contains the active API, it has the advantage that effective efficacy can be expected when administered to a patient.

This disclosure concerns the treatment of wounds. Disclosed herein are compositions and methods for treating wounds, in particular chronic wounds, using caspase-3 inhibitors. Also disclosed are methods of detecting wounds based on levels of cleaved caspase-3 and / or caspase-3 activity in a wound sample.

The present invention relates to a preparation for injection including an isoxazoline derivative useful as a caspase inhibitor or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient (API).The preparation for injection according to the present invention includes the first solution composed of a high-dose API and the second solution including a reconstitution solution, so that it can be prepared by mixing the first formulation and the second formulation immediately before administration to a patient, and contains the Active-API stably. Therefore, there is an advantage that effective drug efficacy can be expected when administered to a patient.

A growing number of patients presenting severe combined immunodeficiencies associated with Rac2 mutations have been identified in newborns. These mutations are associated with high frequency of infection, leukopenia and more rarely autoinflammatory features. Here, the inventors show that the Rac2 activating mutations activates the NLRP3 inflammasome leading to the secretion of IL-1β from macrophages depending on the mutated RAC2 activation strength. Therefore, inhibiting the Rac2-PAK1 / 2-NLRP3 inflammasome pathway should be considered as a potential treatment for these patients. The present invention relates to a method of treating Rac2 monogenic disorders in a subject in need thereof comprising the administration of an inhibitor of NLRP3 and / or an inhibitor of PAK1 / 2 and / or an inhibitor of caspase 1.

A method for treating or reducing the severity of neurodevelopmental defects in a developing nervous system after exposure to an anesthetic by modulating or inhibiting caspase activity, for example, by administering a pan-caspase inhibitor such as pan-caspase inhibitor Q-VD-OPh to a subject having or at risk of congestive heart disease and / or having a ciliopathic disorder.

To provide compounds that are caspase inhibitors, pharmaceutical compositions containing these compounds, and methods of using such compounds and pharmaceutical compositions.SOLUTION: Provided herein are compounds of formula (I), compositions comprising the compounds, and methods of treating various diseases by means of the compounds and compositions.SELECTED DRAWING: Figure 1

The cell stabilizer is prepared from the following components in concentration: 3 to 10 percent (w / v) of a cell separating agent, 3 to 8 mu M of a caspase inhibitor, 0.33 to 0.40 mM of mimic peptide, 3.35 to 7.25 mM of alpha-D-glucose, 0.50 to 1.50 mM of N-acetyl-L-cysteine, 2 to 15 mM of NaCl, 0.02 to 90 mu g / ml of a platelet inhibitor and 20 to 40 mM of anhydrous sodium acetate. According to the cell stabilizer provided by the invention, the preservation time of a whole blood sample after being in vitro can be prolonged, so that the detection duration of the collected sample of the detection kit can be prolonged, and the stability of an ATP detection value of the detection kit can be ensured.

The invention relates to the technical field of cell cryopreservation, and discloses a blastocyst vitrification refrigerating fluid set and application, the refrigerating fluid set comprises a basic buffer solution, a composite permeable protective agent, a non-permeable protective agent, a thermosensitive macromolecule regulating agent, a molecular state locking agent, a zwitterionic osmotic pressure buffer agent, a cell apoptosis inhibitor and an efficient antioxidant, the invention further provides a preparation method of the blastocyst vitrification refrigerating fluid set. The preparation method comprises the following steps: weighing HEPES in a clean container; gradually adding ethylene glycol and dimethyl sulfoxide into the basic buffer solution according to a ratio of 1: 1; slowly adding trehalose into the mixed liquid; slowly adding poloxamer into the transparent solution; then adding chondroitin sulfate; proline is gradually added; the preparation method comprises the following steps: adding a generic caspase inhibitor Z-VAD-FMK; and then adding the L-glutathione. According to the method disclosed by the invention, the blastocyst is subjected to cryoprotection by adopting the impermeable protective agent trehalose, so that the cell survival rate is remarkably improved.

The invention relates to the technical field of biology, in particular to a gene editing method of neutrophil. The method comprises the following steps: carrying out electrotransfection on neutrophils; then resuspending the neutrophils subjected to electrotransfection in a cell culture solution, and culturing in an incubator under a standard condition to realize gene editing. The cell culture solution is prepared by taking a universal caspase inhibitor and a growth factor as main bodies, supplementing a lysosomal membrane permeation inhibitor, a cell oxidation inhibitor and a cell necrosis inhibitor, and matching with an RPMI culture solution and fetal calf serum as solvents. The transfected gene can be effectively expressed in the neutrophil for a long time, the transfection efficiency can reach 78% at most, gene editing of the neutrophil is achieved, and the immunocompetence of the cell can be kept for a long time within 5 days after transfection; the problem of gene editing of the neutrophile granulocytes in the fields of life science and medicine at present is solved, and a basis is provided for further research of the neutrophile granulocytes.

Herein is reported a method for producing a recombinant adeno-associated viral particle (rAAVp) preparation comprising the steps of cultivating a mammalian cell comprising a gene encoding a non-adeno-associated-virus gene, which is operably linked to two AAV inverted terminal repeats (ITRs) (i.e. the non-adeno-associated virus gene is interspaced between the two AAV ITRs), a gene encoding the AAV Cap protein VP1 and / or VP3, a gene encoding the AAV Rep protein Rep78 or Rep68 and / or a gene encoding the AAV Rep protein Rep52 or Rep40, a gene encoding the adenoviral helper function E4orf6, and a gene encoding the adenoviral helper function E2A, recovering the rAAVp from the cell and / or the cultivation medium, and thereby producing the rAAVp preparation, whereby the cultivating of the mammalian cell is in the presence of at least one compound selected from one of the following groups of compounds the caspase inhibitor Q-VD-OPh and IDN6556, DNA damage response activation inducing substances, including ATM / ATR inducing substances, antiviral response inhibitors, AMPK activators, oxidative phosphorylation agents, inhibitors of κB kinase, dNTP synthesis enhancers, including co-factors and building blocks, and cell cycle modulators.

The invention provides a compound of Formula (I): or a salt thereof, wherein R1-R7, X, Y, and Ra-Rz have any of the values described in the specification, as well as compositions comprising a compound of Formula (I). The compounds are useful as caspase-2 inhibitors.

The invention relates to the field of cancer therapy, especially by inducing cell death of malignant B cells by activating RIPK3 signaling pathway in these cells. The invention thus involves activating RIPK3 signaling pathway in malignant B cells for treating a patient in need thereof. The activation of RIPK3 signaling pathway in malignant B cells has in particular been shown to be beneficial against tumor growth, in particular when combined with an agonist of MLKL (like type I IFN) and / or a caspase inhibitor that optimize direct tumor cell death and subsequent anti-tumor immune response.

The invention relates to the technical field of biology, in particular to a cryopreservation and recovery method of neutrophil. According to the invention, a universal caspase inhibitor and a growth factor are used as main bodies, a lysosomal membrane permeation inhibitor, a cell oxidation inhibitor and a cell necrosis inhibitor are used as auxiliary materials, different solvents are matched to respectively prepare a cell culture solution and a cell cryopreservation solution, and effective cryopreservation and resuscitation procedures are added, so that the in-vitro preservation time of neutrophils is greatly prolonged; furthermore, long-time in-vitro high-activity effective cryopreservation and recovery of the neutrophile granulocytes are realized; wherein the RPMI culture solution and the fetal calf serum are used as solvents of the cell culture solution, and the serum-free cryopreservation solution is used as a solvent of the cell cryopreservation solution. Compared with a common culture medium preservation method, the cryopreservation resuscitation method provided by the invention has the advantages that the activity of the neutrophile granulocyte can be better maintained, the activity retention rate of the resuscitated neutrophile granulocyte stored for 14-21 days is greater than or equal to 96%, technical support is provided for application of the neutrophile granulocyte, and thus the cryopreservation resuscitation method has a good industrialization prospect.

The invention discloses a technology for inducing mitochondrial membrane damage and an autophagy degradation mechanism based on Raptinal. The technology is used for reducing the content of residual mutation mtDNA carried in the mitochondrial replacement process. According to the method, before nuclear transfer (PNT), a nuclear donor embryo containing mutated mtDNA is placed in a Raptinal operating solution for short-time incubation, so that a mutated mitochondrial membrane is depolarized and damaged, and then the mutated mitochondrial membrane is selectively cleared through the mitochondrial autophagy effect of a nuclear receptor embryo, so that the co-transfer of the mutated mtDNA is remarkably reduced. And cell apoptosis is avoided by adding a pan-caspase inhibitor, so that the balance between membrane injury and embryo survival is realized. C57BL / 6J and BALB / c mice are taken as models, allele-specific PCR (polymerase chain reaction) is used for detecting mtDNA residues of reconstructed embryos, and results show that the detection rate of mutated mtDNA can be reduced from 100% to 30% and the carrying rate of the mutated mtDNA is reduced by more than 70% through Raptinal treatment. The method is easy and convenient to operate, safe, reliable and suitable for the mammalian mitochondrial replacement process, and an efficient new scheme is provided for preventing maternal mitochondrial genetic diseases.

Up-regulation of caspase has been found in COVID-19 patients, and also occurs in patients suffering from diabetes, hypertension, metabolic syndrome, and other conditions. Such up-regulation can be responsible for poor clinical outcomes in patients having such diseases or disorders, as such up-regulation leads to a process called pyroptosis: death and malfunction of immune system cells, particularly of certain types of lymphocytes. An inhibitor of caspase such as a caspase 1 inhibitor, or “pan-caspase” inhibitor (i.e., an inhibitor of multiple caspase types including caspase-1), can be used to treat COVID-19 patients or individuals at risk of infection, by limiting the malfunction of the immune system. A caspase-1 or pan-caspase inhibitor is advantageously administered before or very early in the course of infection by a positive-sense, single-stranded RNA virus such as SARS-COV, MERS-COV, or SARS-Cov-2.

The present invention provides a novel isoindolinone derivative compound as a caspase inhibitor, a hydrate thereof, a solvate thereof, or a pharma- ceutically acceptable salt thereof. The novel isoindolinone derivative compound of the present invention has been confirmed to exhibit excellent activity as a caspase inhibitor by exhibiting excellent interleukin-1β (IL-1β) reducing effect and excellent apoptosis reducing effect, and therefore it has been revealed that it can be used for preventing or treating caspase-related diseases. Therefore, the novel isoindolinone derivative compounds of the present invention can be usefully used in the fields of medicine and pharmaceutical science for the prevention or treatment of caspase-related diseases.

The invention relates to the technical field of immune cells, and discloses a high-activity immune cell cryopreservation method and a high-activity immune cell recovery method. The cryopreservation protective agent is prepared from the following raw materials in percentage by volume: 8 to 12 percent of dimethyl sulfoxide, 5 to 8 percent of trehalose, 5 to 10 percent of dextran 40 to 60, 2 to 4 percent of human serum albumin, 0.1 to 0.5 percent of a cell factor mixture, 3 to 6 percent of an active protective agent and the balance of a basic culture medium. According to the invention, trehalose, dextran 40-60 and an active protective agent composed of a mitochondrial targeting antioxidant SS-31, a caspase inhibitor Z-VAD-FMK and membrane stability polypeptide are introduced, and the concentration and addition mode of dimethyl sulfoxide are strictly controlled, so that the damage of a traditional cryopreservation protective agent to cells due to osmotic pressure impact and chemical toxicity can be reduced.

The present invention relates to a pharmaceutical formulation for injection comprising an isoxazoline derivative useful as a caspase inhibitor or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient (API). The pharmaceutical formulation for injection according to the present invention includes the first formulation composed of a high-dose API and the second formulation including a reconstitution solution, so that it can be prepared by mixing the first formulation and the second formulation immediately before administration to a patient, and contains the Active-API stably. Therefore, there is an advantage that effective drug efficacy can be expected when administered to a patient.