81 results about "GPX4" patented technology

According to the GPX4 protein degradation agent and the application, the degradation agent serves as molecular glue to induce tumor cell ferroptosis and is different from an existing PROTAC technology, and the molecular glue can induce interaction between E3 ubiquitin ligase and target protein GPX4 and promote ubiquitination of the E3 ubiquitin ligase and the target protein GPX4. Compared with the existing GPX4 degradation agent, the molecular glue has the advantages of small molecular weight, high cell permeability and better druggability. The GPX4 molecular glue disclosed by the invention can be used for effectively degrading GPX4 and has a killing effect on various tumor cell lines. The preparation method is simple in synthesis route and mild in reaction condition, can be used for being developed into a new generation of GPX4 targeting drugs, and has great clinical application value and considerable market potential.

The invention discloses a nanocomposite HA / PEI / Fe3O4 (at) siRNA and a preparation method and application thereof, and belongs to the technical field of antitumor drugs. The nano-composite HA / PEI / Fe3O4 coated siGPX4 is successfully prepared, the serum stability is high, the blood compatibility is good, siGPX4 can be efficiently released when the nano-composite reaches a tumor acidic microenvironment, then the anti-tumor effect is exerted, triple negative breast cancer cells can be specifically targeted, the internalization ability of MDA-MB-468 cells on the nano-composite is greatly improved, and the delivery efficiency of siGPX4 is remarkably improved; in the presence of H2O2, the nano-composite can down-regulate expression of GPX4, released ferrous ions and H2O2 are subjected to Fenton reaction, ROS in cells is remarkably increased, mitochondrial membrane potential is reduced, ferroptosis is triggered, MDA-MB-468 cell proliferation is remarkably inhibited, and the anti-tumor effect is achieved.

The invention belongs to the technical field of medicine preparation, and particularly relates to application of DHGC in preparation of a medicine for treating acute kidney injury ferroptosis mediated by an SIRT3 / NRF2 axis. Experiments prove that DHGC can activate SIRT3 in a targeted manner, up-regulate the expression level of SIRT3, promote NRF2 deacetylation and drive NRF2 nuclear translocation, and further up-regulate the expression level of GPX4, so that the effect of resisting ferroptosis caused by acute kidney injury is achieved.

The invention discloses an application of an METTL3 small-molecule inhibitor STM2457 in preparation of a medicine for treating gastric cancer. The STM2457 specifically induces ferroptosis of gastric cancer cells through the m6A-GPX4 axis, compared with RSL3, the STM2457 has the advantages that the toxicity of the STM2457 to normal cells is reduced by about 30%, the targeting property is clear, the curative effect and the safety are both achieved, and a theoretical basis and experimental data support are provided for clinical development of METTL3 targeted drugs.

The embodiment of the invention discloses application of ALDH3A2 as a target spot in preparation of a medicine for treating gastric cancer. The research clarifies a new effect and a potential mechanism of ALDH3A2 in the aspect of inhibiting gastric cancer progression. Specifically, the ALDH3A2 can be used for down-regulating the expression of SLC47A1, so that the nuclear transfer of NRF2 is prevented, and the activation of UPRmt is inhibited. The damage can aggravate mitochondrial dysfunction, and finally, gastric cancer cell ferroptosis is promoted in a glutathione peroxidase 4 (GPX4) dependent mode. In addition, ferroptosis induced by ALDH3A2 can also promote polarization of macrophages to M1 type, and the progress of gastric cancer cells is inhibited through an IL-1beta signal channel. In conclusion, the effects jointly inhibit proliferation, migration and invasion of gastric cancer cells, and finally inhibition of growth and metastasis of gastric cancer is achieved.

This invention discloses a pharmaceutical composition for treating asthenospermia by activating the Nrf2 / HO-1 / GPx4 pathway and its application. The pharmaceutical composition comprises taurine and geranium as active ingredients, wherein the mass ratio of taurine to geranium is 3-5:1. The pharmaceutical composition of this invention can synergistically activate the Nrf2 / HO-1 / GPx4 antioxidant signaling pathway, upregulate the expression of downstream antioxidant enzymes GPx4 and HO-1, inhibit lipid peroxidation, protect sperm mitochondrial function, and simultaneously improve the microenvironmental metabolic profile of the epididymis—the site of sperm maturation—thereby enhancing sperm motility. The pharmaceutical composition provided by this invention can be used to prepare a treatment for asthenospermia, particularly oxidative stress-induced asthenospermia.

The application provides a nano-catalytic material system capable of targeting tumors for gene editing, which is obtained by loading a CRISPR / Cas9 plasmid of a gene editing system capable of editing a core protein gene GPX4 related to cell ferroptosis into the pores of an iron single-atom nano-catalyst, and then modifying the cell membrane of a homologous tumor. The nano-catalytic material system provided by the application has excellent Fenton catalytic performance, can accurately edit target genes, induces tumor cells to undergo ferroptosis, and has the advantages of simple synthesis process, low cost, easy batch production, high enrichment degree at a lesion site, good treatment effect, and good clinical application prospect.

The invention discloses a traditional Chinese medicine composition for treating sarcopenia by regulating a CXCR4 / GPX4 axis to inhibit ferroptosis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-15 parts of eucommia ulmoides, 5-15 parts of herba epimedii, 5-15 parts of fructus psoraleae and 5-15 parts of semen cuscutae. The traditional Chinese medicine composition disclosed by the invention has the traditional effects of tonifying kidney, strengthening yang and strengthening tendons and bones, and is proved to be capable of promoting GPX4 expression and inhibiting ferroptosis of muscle cells by up-regulating CXCR4 expression, so that muscle strength is effectively enhanced, proliferation and differentiation of muscle satellite cells are promoted, oxidative stress is reduced, and the traditional Chinese medicine composition is used for preventing or treating sarcopenia.

The invention provides a GPX4 protein-bound polypeptide derivative, a condensation body formed by the GPX4 protein-bound polypeptide derivative and application of the GPX4 protein-bound polypeptide derivative. Specifically, the invention provides a GPX4 protein-bound polypeptide derivative, the structural formula of which is shown in the following formula (I): in the formula (I), R1 is a GPX4 binding unit, and R2 is a linker. The polypeptide derivative can effectively inhibit the growth of GPX4 high-expression tumors, inhibit the metastasis of the tumors and degrade GPX4 protein in tumor tissues, so that the polypeptide derivative can be developed into drugs for treating the GPX4 high-expression tumors. (I).

The invention discloses application of RMTE in preparation of a medicine for preventing and controlling grass carp reovirus. The hemorrhagic disease caused by the grass carp reovirus (GCRV) is a key bottleneck restricting healthy development of the grass carp breeding industry, and the current vaccine for treating the grass carp reovirus (GCRV) has the problems of unstable immune protection effect, low protection rate for crossing of strains of different genotypes and the like, so that the research and development process of antiviral drugs is slow. The invention discloses an influence and a potential mechanism of a rhodamine B-ethyl sulfide condensation compound (RMTE) on GCRV (Growth Factor Receptor Virus) infection. Results show that the RMTE can significantly inhibit expression of VP6 and VP7 genes in GCRV infected cells, can effectively relieve expression inhibition of GCRV on GPX4, Caspase and p53 genes and promote expression of the three genes, and prove that the RMTE has a significant inhibition effect on GCRV infection and plays an antiviral effect through multiple ways. Research results provide new potential drugs and theoretical basis for prevention and control of GCRV.

The invention relates to a novel ferrocenyl hydrophobic label degradation agent targeting GPX4 as well as a preparation method and application of the novel ferrocenyl hydrophobic label degradation agent. The GPX4 protein degradation agent has a chemical structure as shown in a formula (I). Pharmacological experiments show that the derivative or salt disclosed by the invention can be used for remarkably degrading GPX4 protein in ferroptosis sensitive cells (such as HT1080, OS-RC-2, 4T1 and 786-O), and has very strong anti-proliferative activity on the four cell strains. The invention also provides a preparation method of the derivative and the pharmaceutically acceptable salt thereof, and an application of the derivative and the pharmaceutically acceptable salt thereof as a GPX4 degradation agent. Formula (I).

The invention belongs to the technical field of medicine preparation, and particularly relates to a ferroptosis agonist, an anoxia response type nanometer co-delivery system and application thereof. The novel ferroptosis agonist RSL3-ClAc is synthesized by introducing a chloracetyl fragment into an RSL3 molecule, the binding capacity of the novel ferroptosis agonist RSL3-ClAc with GPX4 is remarkably enhanced, and then the ferroptosis induction efficiency is improved. And meanwhile, the RSL3-ClAc and the hypoxia response type photosensitizer TCy5-NO2 are subjected to self-assembly, so that the nano drug delivery system is constructed. According to the nano drug delivery system, the EPR effect and the hypoxia response characteristic of the nano carrier are utilized, the tumor barrier can be effectively broken through, and the focus can be accurately positioned. In a tumor hypoxic microenvironment, the activation of a Try5-NO2 photosensitizer is triggered by nitroreductase (NTR), and RSL3-ClAc is synchronously released to enhance the ferroptosis induction effect.

The present invention discloses a semicarbazide derivative and its preparation method and application, which belongs to the technical field of anti-lung cancer targeted drugs. The semicarbazide derivative of the present invention can inhibit the growth of H1299 cells in a dose-dependent manner, but has little toxicity to normal lung epithelial cells BEAS-2B. The semicarbazide derivative of the present invention can significantly inhibit the cloning of non-small cell lung cancer cells A549 and H1299, so it has a significant inhibitory effect on the proliferation of non-small cell lung cancer. The semicarbazide derivative provided by the present invention can inhibit the protein expression of GPX4 in non-small cell lung cancer A549 cells, and by inhibiting the protein expression of GPX4, promote the ferroptosis of non-small cell lung cancer cells, thereby playing a role in suppressing tumors.

The invention discloses a preparation method of a radix tetrastigme extract and an application of the radix tetrastigme extract in a medicine for inhibiting epithelial cell ferroptosis and pyroptosis in double ways, and mainly discloses an application of the radix tetrastigme extract in a medicine for inhibiting epithelial cell ferroptosis and pyroptosis in double ways. Comprising the following components: kaempferol-3-carveosyl glucose-7-rhamnoside and kaempferol-3-glucose-7-rhamnoside. In the technical scheme, the radix tetrastigme root hair extract can inhibit an SLC7A11 / GPX4 signal channel and an NLRP3 / GSDMD signal channel at the same time by up-regulating the protein expression levels of SLC7A11 and GPX4 and down-regulating the protein expression levels of NLRP3 and GSDMD-N at the same time, so that the radix tetrastigme root hair extract has a double-channel inhibition effect on ferroptosis and pyroptosis of epithelial cells at the same time; according to the scheme, the unique kaempferol-3-apiosyl glucose-7-rhamnoside and kaempferol-3-glucose-7-rhamnoside are extracted from the radix tetrastigme root hair, the extraction process is optimized, and the radix tetrastigme root hair with high purity is obtained through separation and effectively utilized.

Provided are a cancer therapeutic drug comprising a compound which inhibits GPX4 as an active ingredient, the cancer therapeutic drug treating cancer containing a cancer cell having a suppressed function of a SWI / SNF complex factor detected; and a method for predicting sensitivity of a cancer cell to a GPX4 inhibitor, the method comprising the step of predicting a cancer cell having a suppressed function of a SWI / SNF complex factor detected in the cancer cell, as having sensitivity to the GPX4 inhibitor.

The present invention provides a flavonoid compound and a preparation method and application thereof, a pharmaceutical composition and application thereof, and relates to the field of biomedicine technology. The flavonoid compound provided by the present invention has excellent antioxidant activity and significant GSH-Px activation effect, has low toxicity and high efficiency, is suitable for preparing a variety of antioxidant drugs and drugs for treating diseases related to oxidative stress, has broad clinical application prospects and important drug development value, will promote the progress of flavonoid drug research and development, and provide new solutions for antioxidant therapy. In vitro experiments and cell model verification show that: in HUVECs and AML12 cell lines, compared with kaempferol, the flavonoid compound provided by the present invention significantly increased the activity of GPX4 and its protein expression level; the ability to scavenge DPPH free radicals is significantly higher than that of kaempferol, and the antioxidant property is significantly better than that of kaempferol; the toxicity to AML12 cells is significantly lower than that of kaempferol.

The present invention provides a method for constructing an animal model of systemic lupus erythematosus, belonging to the technical field of methods for constructing disease animal models. In the present invention, mice GPX4<supgt;fl / wt< / supgt;VilCre+ containing heterozygous GPX4 gene and Cre gene are first obtained, and then SLE induction drugs are used to further induce the mice to develop the disease. In view of the specific gene knockdown in specific cells in the present invention, the etiology of the disease development in the model is clear, that is, the abnormal intestinal barrier system triggers adaptive immune changes, recognizes autoantigens, and ultimately leads to the development of lupus. At the same time, the finally obtained SLE model in the present invention can exhibit higher autoantibodies, lower complement, higher inflammatory factors, and more severe lung damage, and the decrease of intestinal GPX4 in these mice is similar to the intestinal expression characteristics of human SLE.

The application provides a kind of PARP and GPX4 double-target inhibitor and its preparation method and application, the PARP and GPX4 double-target inhibitor has the structure as shown in general formula I, specifically, the application provides a kind of compound with the structure shown in general formula I.The compound has good PARP and GPX4 double-target inhibitory activity, and thus can be used for treating diseases related to abnormal expression or activity of PARP and GPX4, in particular for treating breast cancer and ovarian cancer and other malignant tumors.

The invention relates to a GPX4 protein inhibitor as well as a preparation method and application thereof. Specifically, the present invention relates to compounds of formula (I), pharmaceutically acceptable salts, N-oxides, hydrates, solvates, metabolites, polymorphs or prodrugs thereof, or tautomers, meso, racemes, enantiomers, diastereoisomers thereof, or mixtures thereof, the compound as shown in the formula (I) or the pharmaceutical composition thereof can selectively interfere with the activity of GPX4 so as to induce ferroptosis of tumor cells.

To develop a therapeutic strategy capable of specifically targeting cancer cells in which depression of the function of the SWI / SNF complex occurs, and more specifically, to develop a therapeutic strategy that specifically targets cancer cells in which depression of the function of an SWI / SNF complex factor is detected.SOLUTION: A therapeutic agent for cancer comprising, as an active ingredient, a compound that inhibits GPX4 and containing a cancer cell in which depression of the function of an SWI / SNF complex factor is detected, and a method for predicting the sensitivity of a cancer cell to a GPX4 inhibitor, the method comprising a step for predicting a cancer cell in which depression of the function of an SWI / SNF complex factor is detected as having sensitivity to the GPX4 inhibitor.SELECTED DRAWING: None

The present disclosure provides methods for treating cancer using ferroptosis inducers in combination with one-carbon metabolism inhibitors. The combination of ferroptosis inducers and one-carbon metabolism inhibitors induce greater ferroptosis than treatment with either alone. In certain embodiments, the one-carbon metabolism inhibitors are serine hydroxymethyltransferase (SHMT) inhibitors and / or methylenetetrahydrofolate dehydrogenase (MTHFD) inhibitors. By way of example, the ferroptosis inducers are GPX4 inhibitors.

The invention provides an application of selenomethionine in preparation of a medicine for preventing and / or treating cisplatin-induced acute kidney injury. The selenomethionine can resist ferroptosis without depending on GPX4, and plays a role in kidney protection. The mechanism not only comprises providing a selenium source for GPX4 synthesis through a non-sulfur conversion way, but also has the capability of directly removing reactive oxygen species (ROS) independent of GPX4, thereby achieving the effect of dual inhibition of ferroptosis. Animal experiments prove that selenomethionine can remarkably improve the renal function of a cis-platinum induced acute kidney injury model mouse and relieve tissue injury. The invention provides a new potential treatment strategy for clinical prevention and treatment of acute kidney injury caused by cisplatin and other drugs.

A method of using CST1 and GPX4 as a gastric cancer metastasis marker or prognostic marker. The method detects the protein expression of CST1 and GPX4, draws an ROC curve using SPSS software, obtains the sensitivity and specificity of the diagnosis, and calculates the area under the curve AUC value. Finally, the gastric cancer samples are classified according to the AUC value, sensitivity and specificity, and applied to the diagnosis of gastric cancer metastasis. CST1 and GPX4 are used as markers for joint detection of gastric cancer, and the detection has strong specificity and high sensitivity, which can effectively avoid false positive or false negative results that are prone to occur when CST1 or GPX4 is used alone as a diagnostic marker, and provide reliable information for the early diagnosis of gastric cancer metastasis. The method draws a survival curve through follow-up and survival analysis, determines that patients with double positive results of CST1 and GPX4 have a worse prognosis, and provides a biomarker for predicting the prognosis of gastric cancer. The present invention provides a combined biomarker for early diagnosis and prognosis of gastric cancer metastasis with strong specificity and high sensitivity, and its application.

Provided are a cancer therapeutic drug comprising a compound which inhibits GPX4 as an active ingredient, the cancer therapeutic drug treating cancer containing a cancer cell having a suppressed function of a SWI / SNF complex factor detected; and a method for predicting sensitivity of a cancer cell to a GPX4 inhibitor, the method comprising the step of predicting a cancer cell having a suppressed function of a SWI / SNF complex factor detected in the cancer cell, as having sensitivity to the GPX4 inhibitor.

The present invention belongs to the technical field of anticancer drugs, and specifically relates to artesunate PROTAC derivatives, compositions and applications with GPX4 degradation activity, with the structural formula being as follows: #imgabs0#; wherein R is a Cereblon protein ligand or a VHL protein ligand, and the linker is a connecting group between artesunate and R; the present invention improves the anti-tumor effect thereof.

The invention discloses a compound capable of inducing cell ferroptosis and a preparation method and application thereof. The compound not only can promote Fe < 2 + > accumulation to trigger iron overload, but also can inhibit GPX4 protein expression to cause accumulation of peroxides in cells and synergistically enhance the ferroptosis effect. The compound has remarkable ferroptosis induction activity on various abnormal hyperplasia cells, shows broad-spectrum anti-tumor potential and has an important clinical application prospect.

The application discloses a chimeric body based on targeted degradation of GPX4 mediated by a molecular chaperone HSP90 and a preparation method and application thereof, and belongs to the technical field of biological medicines. Five chimeric bodies for targeted degradation of GPX4 are prepared by using the technology. The molecular chaperone HSP90 mediated protein targeted degradation chimeric body disclosed by the application can effectively induce degradation of GPX4, thereby triggering ferroptosis. Meanwhile, the chimeric body has obvious anti-proliferation activity on cell strains with high expression of GPX4, and has important significance for tumor targeted therapy.

The invention provides application of bufalin based on an MDM2-GPX4 regulatory pathway in preparation of non-small cell lung cancer resisting drugs, and relates to the technical field of biological medicines. According to the application, the medicine induces non-small cell lung cancer cells to generate ferroptosis through an MDM2-GPX4 regulatory pathway, so that occurrence and development of the non-small cell lung cancer are inhibited, the non-small cell lung cancer is p53 mutant non-small cell lung cancer, bufalin is directly combined with MDM2 to play a role of molecular glue, MDM2 and GPX4 are promoted to form an interaction compound, and the non-small cell lung cancer can be effectively inhibited. Further, GPX4 function inhibition or degradation is mediated, and ferroptosis is induced. The GPX4 is regulated through the E3 ubiquitin ligase function of the MDM2 for the first time, p53 mutant NSCLC can be effectively treated without relying on p53 activity, the problem that the application range of a traditional MDM2 inhibitor is limited is solved, the mechanism is clear, a bufalin (drug)-MDM2 / GPX4 (target)-ferroptosis (pathway) three-level regulation network is illuminated, and the uncertainty and risk of clinical development are reduced.

The invention discloses application of fluoxetine in preparation of a medicine for treating epileptic seizure or brain injury. In-vivo and in-vitro experiments find that fluoxetine can inhibit epilepsy-induced ferroptosis by inhibiting ubiquitination of GPX4 protein so as to play a role in treating epileptic seizure or brain injury for the first time, and a new technical means is provided for treatment of epilepsy or brain injury.