19 results about "Uncoupling Agents" patented technology

The invention discloses a loose macroporous iron-based nano catalytic compound for inducing tumor para-apoptosis and a preparation method and application thereof.The nano catalytic compound (TF-Fe at LC) is prepared by taking a porous Fe3O4 nano cluster composed of single crystals as a carrier, modifying the surface of the carrier with an acid-responsive tannic acid-iron (TA-Fe < 3 + >) network and co-loading lactate oxidase (LOD) and a mitochondrial uncoupling agent CCCP in the carrier. The TF-Fe-coated LC constructed by the invention does not need additional chemotherapeutic drugs, and tumor cells are induced to generate a large amount of active oxygen through catalytic cascade and mitochondrial oxidative stress, so that parapoptosis of the tumor cells is triggered; the parapoptotic cells can play a role of a tumor vaccine, induce other tumor cells to generate immunogenic death, and activate an organism immune system to recognize and kill tumors. In addition, the nano catalytic system can be combined with drugs and immunosuppressants to realize a synergistic anti-tumor effect.

The disclosure provide compounds of Formula I and the pharmaceutically acceptable salts thereof. The variables, R1, R2, R3, X1, X2, and Z are defined herein. Certain compounds of Formula I act as selective mitochondrial protonophore uncouplers that do not affect the plasma membrane potential. Compounds and salts of Formula I are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH). Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, compounds of Formula I are useful for increasing lifespan. Compounds and salts of Formula I are also useful for regulating glucose homeostasis or insulin action in a patient.

Provided herein are anti-overdosing compositions and uses thereof. Specifically, provided herein are anti-overdosing pharmaceutical compositions comprising a mitochondrial uncoupler and a GLP-1R agonist and uses thereof as well as methods for preventing overdosing of the uncoupler. Such pharmaceutical compositions can be useful for treating diseases, such as but not limited to NASH, overweight, obesity, medical complications related to overweight or obesity, type 2 diabetes (T2D), and Alzheimer's disease and related dementias (AD / ADRD).

We provide safe mitochondrial uncoupling agents. [Solution] The present invention provides 5-[(2,4-dinitrophenoxy)methyl]-1-methyl-2-nitro-1H-imidazole, a novel phenyl derivative, or a pharmaceutically acceptable salt thereof. This compound is useful for regulating mitochondrial activity, reducing obesity, and treating diseases including diabetes and diabetic complications.

The present application belongs to the technical field of animal model construction, and relates to a insomnia animal model construction method and application with the characteristics of body deficiency, fever and emotional irritability. The application of uncoupling agent as a modeling agent in the construction of insomnia animal model with the characteristics of body deficiency, fever and emotional irritability; the uncoupling agent is carbonic acid cyanide-4-trifluoromethoxy benzyl hydrazone, carbonyl cyanide m-chlorophenyl hydrazone or benzalazoline. The present application uses mice as model animals, uses uncoupling agent as a modeling agent, and suspends or dissolves the modeling agent, then gives the mice intragastric administration once a day, and lasts for 1-4 weeks, to construct a "deficiency and irritability insomnia" insomnia animal model with the characteristics of body deficiency, fever and emotional irritability. The present application has a high degree of consistency with the traditional Chinese medicine theory, and can be well used for the screening and evaluation of anti-insomnia chemical drugs, anti-insomnia traditional Chinese medicine compounds and anti-insomnia health care products.

The invention relates to the technical field of biological engineering, and discloses a method for producing agricultural tryptophan through fermentation and application, and the method comprises the following steps: after thalli are accumulated, adding L-serine in a pulse manner, switching to double-carbon-source material supplementation of glucose and glycerol, and starting energy metabolism uncoupling control at the same time; according to the energy metabolism decoupling control, a decoupling agent is fed, a real-time respiration quotient is used as a feedback signal, and a closed-loop system is used for automatically adjusting the flow acceleration rate, so that the respiration quotient is maintained in a target range. According to the invention, intracellular energy charge is reduced through uncoupling so as to relieve glycolysis inhibition and strengthen carbon flux, double carbon sources are utilized to maintain redox balance, and pulse feeding is matched to eliminate terminal synthesis bottleneck. According to the method, the metabolic competition problem of cell growth and product synthesis is effectively solved, the conversion rate and fermentation yield of tryptophan are effectively improved, and the obtained product is suitable for preparing an agricultural fertilizer synergist or a feed additive.

This invention discloses a mitochondrial uncoupling agent prodrug with endothelial cell targeting, its preparation method, and its application, relating to the field of biomedical technology. The prodrug is covalently coupled to a vascular cell adhesion molecule-1 targeting polypeptide (amino acid sequence FAKELMEEFEKW), a reactive oxygen species-sensitive thioacetate linker, and the mitochondrial uncoupling agent OPC-163493. This invention utilizes the active enrichment effect of the targeting polypeptide on inflamed pulmonary vascular endothelial cells, overcoming the off-target defects of non-specific distribution in existing small molecule drugs; simultaneously, it utilizes the specific cleavage characteristics of the thioacetate linker in a microenvironment rich in reactive oxygen species to achieve precise in-situ drug release. This prodrug can effectively reduce mitochondrial reactive oxygen species generation, inhibit endothelial cell apoptosis, significantly reduce pulmonary vascular permeability, and alleviate pulmonary edema, possessing significant clinical application value in the preparation of drugs for treating acute lung injury or acute respiratory distress syndrome.

This invention relates to the field of tissue engineering technology, specifically disclosing a deer placental stem cell exosome and its preparation method. The invention uses deer placental chorionic villus tissue as raw material, and obtains highly active stem cells through mild enzymatic hydrolysis, differential adhesion, and purification in a metabolically stable culture medium. Serum-free stress induction is performed using the mitochondrial uncoupling agent FCCP, combined with differential centrifugation, double-layer filtration, gradient density centrifugation, and ultrafiltration concentration to achieve efficient purification. Stable exosomes are obtained through vitamin E polyethylene glycol succinate-soybean lecithin complex modification. The preparation process of this invention is mild, scalable, and the resulting exosomes exhibit strong antioxidant and cell proliferation-promoting abilities, high stability, and good bioavailability, making them suitable for tissue regeneration and repair, anti-inflammatory and anti-aging applications, skin care, and stem cell culture additives.

The invention relates to application of a mitochondrial uncoupling agent to preparation of a medicine for treating injury caused by ischemia reperfusion. The injury caused by ischemia reperfusion is cerebral apoplexy or ischemic myocardial injury. The medicine prepared from the mitochondrial uncoupling agent can radically inhibit ROS outbreak by reducing mitochondrial membrane potential and reduce neuron cell area loss and apoptosis, thereby promoting protection of neurons in an ischemic penumbra region; in addition, apoptosis in ischemic myocardial injury can be reduced, and a new strategy is provided for treatment of diseases such as cerebral arterial thrombosis or ischemic myocardial injury.

Dendrimer-drug compositions have been developed that not only target the reactive inflammatory cells / macrophages in the plaque, but also in the adipose tissue, delivering drugs in a targeted manner to simultaneously and independently address both atherosclerosis and obesity, and associated metabolic disorders.   The dendrimers are preferably glucose dendrimers, hydroxyl-terminated PAMAM dendrimers, or sugar-modified dendrimers, most preferably glucose dendrimers.   The drugs are preferably a PPAR-α agonist; a PPAR-γ agonist; a dual PPAR agonist (e.g., a PPAR- α / γ agonists); a GLP-1 receptor agonist (e.g., semaglutide); a metformin; an SGLT2 agonist, a GIP-1 receptor agonist or antagonist; a dual GLP-1 / GIP-1 receptor agonist (e.g., tirzepatide); a mitochondrial uncoupler (e.g., niclosamide); or a combination thereof. These compositions have the ability to overcome the side effects of current drugs for obesity and heart disease, and open new avenues in addressing these disorders through targeting of selective cells.

Provided are the methods of use and pharmaceutical compositions of mitochondrial uncouplers and glucagon-like peptide-1 receptor agonists for treating various diseases and conditions, including obesity, T2DM, liver diseases and conditions (e.g., MASH), and cardiovascular diseases and conditions(e.g.,heart failure).

Provided herein are pharmaceutical compositions comprising thermoresponsive polymer and uses thereof. Specifically, provided herein are pharmaceutical compositions comprising a mitochondrial uncoupler and a thermoresponsive polymer and uses thereof. Such pharmaceutical compositions can be useful for treating diseases, such as but not limited to NASH, overweight, obesity, medical complications related to overweight or obesity, type 2 diabetes (T2D), and Alzheimer's disease and related dementias (AD / ADRD).

This invention provides a composition comprising (i) a first agent selected from the group consisting of a BH3 mimetic, an HDAC6 inhibitor, and a TLR-1, -2, and / or -4 inhibitor, and (ii) a second agent selected from the group consisting of a mitochondrial uncoupler, a Bcl-2 inhibitor, a p53 / MDM2 inhibitor, a HSP-90 inhibitor, a PI3K / AKT inhibitor, a BET inhibitor, and a general senolytic. This invention also provides related compositions and formulations, methods, and articles of manufacture.

The present invention relates to pesticide mixtures comprising as active compound I a carboxamide derivative active as an insecticide and at least one active compound II selected from group M comprising acetylcholine esterase inhibitors, GABA-regulated chloride channel antagonists, sodium channel modulators, nicotinic acetylcholine receptor agonists / antagonists, allosteric nicotinic acetylcholine receptor activators, chloride channel activators, juvenile hormone mimics, homopteran feeding blockers, mite growth inhibitors, mitochondrial ATP synthase inhibitors, oxidative phosphorylation uncouplers, chitin biosynthesis inhibitors, molting disruptors, ecdyson receptor agonists, octamine receptor agonists, MET inhibitors, voltage-gated sodium channel blockers, lipid synthesis inhibitors,ryanodine receptor modulators and other compounds defined in the description, in synergistically effective amounts. The invention also relates to methods and the use of these mixtures to combat and control insects, arachnids, or nematodes in plants, and to protect these plants against pest infestation, in particular also to protect plant propagation material, such as seeds.

Representative xanthohumol derivatives have been made and have been tested in vivo in mice. Such derivatives have a number of important medicinal benefits, including improving glucose tolerance and decreasing weight gain by increasing energy expenditure and locomotor activity in treated subjects. Disclosed derivatives also may function as mitochondrial uncouplers. Representative compounds include 4-(5-(4-hydroxyphenyl)-1-methyl-1H-pyrazol-3-yl)-5-methoxy-2-(3-methylbut-2-en-1-yl)benzene-1,3-diol and 4-(5-(4-hydroxyphenyl)isoxazole-3-yl)-5-methoxy-2-(3-methylbut-2-en-1-yl)benzene-1,3-diol.

Provided herein are combination therapies involving an AMPK activator, including compounds that are dual AMPK activators and mitochondrial uncouplers, dosed in combination with incretin-based therapies.