42 results about "Sorafenib" patented technology

The invention relates to the field of compounds and biological medicines, and discloses ROS (reactive oxygen species) responsive siRNA (small interfering Ribonucleic Acid) nano-micelles as well as a preparation method and application thereof. According to the invention, a polymer synthesized by adopting a TK-GUA monomer with guanidyl is tightly combined with siRNA through electrostatic interaction, a hydrogen bond and a stable salt bridge structure. Under the action of high-concentration ROS, the ROS response type siRNA nano-micelle disclosed by the invention can be subjected to responsive splitting, so that efficient release of siRNA is realized. Wherein the polymer B has remarkable ROS responsiveness and can trigger release of siRNA under the action of 5 mM hydrogen peroxide, and the regulation and control capability of the polymer B is superior to that of the prior art. The siRNA polymer nano-micelle disclosed by the invention can be combined with sorafenib to realize a synergistic anti-tumor effect.

This invention discloses a eucalyptane-type sesquiterpene dimer compound, its preparation method, and its applications, belonging to the field of pharmaceutical preparation technology. The six eucalyptane-type sesquiterpene dimers (compounds 1-6) disclosed in this invention are novel compounds with defined stereostructures and optically pure composition, exhibiting varying degrees of cytotoxic activity against HepG2, Hep3B, and Huh7 cells. Using sorafenib as a positive control, compounds 1, 5, and 6 showed stronger cytotoxic activity against HepG2 cells than the positive control sorafenib, compound 5 exhibited the strongest cytotoxic activity against Hep3B cells, and compounds 1, 4, 5, and 6 showed stronger cytotoxic activity against Huh7 cells than the positive control sorafenib. Therefore, compounds 1-6 disclosed in this invention have the potential to be developed into anti-hepatocellular carcinoma drugs, showing promising application prospects, and also provide important theoretical support for the further development of Atractylodes macrocephala medicinal plant resources.

The application discloses a novel metabolic marker for preparing a medicine for treating liver cancer and application thereof. By constructing an ALDH6A1 overexpression liver cancer cell line, it is found through detection that the level of methylcitrate in the cell is inversely proportional to the proliferation and migration rate of liver cancer cells. In Aldh6a1 knockout mice, an AKT / NRAS liver cancer model is constructed by high-pressure tail vein injection, and it is found that the content of methylcitrate in the serum is inversely proportional to the levels of ALT and AST in the serum of the mice and inversely proportional to the liver cancer load of the mice. The metabolite methylcitrate can not only effectively inhibit the proliferation of liver cancer cells alone, but also can enhance the inhibitory effect of sorafenib on the proliferation of liver cancer cells. The metabolite can effectively inhibit the formation of tumors, can be used as a metabolic marker for detecting liver cancer, and can more accurately and efficiently judge the severity of liver cancer; and can be used as a novel metabolite for treating liver cancer, and can improve the treatment effect of liver cancer.

This invention discloses the application of epinodoxine in combination with sorafenib in the preparation of drugs for treating liver cancer. Experimental results show that epinodoxine significantly inhibits the proliferation of liver cancer cells and exhibits a good synergistic effect when used in combination with sorafenib, thus reducing toxicity and enhancing sensitization.

The present invention relates to a pharmaceutical composition for preventing or treating cancer, containing 2,6-dichloro-4-(4-(4-hydroxycyclohexylamino)-7H-pyrrolo[2,3-D]pyrimidin-5-yl)phenol as an active ingredient. It has been ascertained that the present invention inhibits the formation of mammospheres in a breast cancer cell line and, when compared to anticancer drugs sorafenib and etoposide, which are topoisomerase inhibitors widely used in lung cancer, ovarian cancer, colon cancer, melanoma and the like, exhibits remarkable effects greater than or equal to those of the anticancer drugs sorafenib and etoposide. In addition, a compound of example 1, according to the present invention, exhibits synergistic anticancer effects when combined with radiotherapy or other anticancer drugs in a breast cancer cell line and a liver cancer cell line, and thus can be developed as an anticancer drug or a food exhibiting excellent effects in the treatment of cancer.

A probiotic composition for treating or preventing metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma(MASLD-HCC) or colorectal cancer, comprises one or more microbiota selected from a group consisting of Lactobacillus helveticus, Lactobacillus plantarum, Lactobacillus rhamnosus GG, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium breve, Bifidobacterium animalis subsp. Lactis, Streptococcus thermophilus or any combination thereof. The probiotic composition demonstrates improved therapeutic effects when combined with low-dose Sorafenib for MASLD-HCC and outperforms 5-Fluorouracil in colorectal cancer models.

This invention discloses the application of MITF inhibitors in the preparation of drugs for the prevention and / or treatment of sorafenib cardiotoxicity, belonging to the field of biomedical technology. This invention is the first to discover that the transcription factor MITF is a core regulatory factor of sorafenib cardiotoxicity. Sorafenib can specifically upregulate the expression and transcriptional activity of MITF in cardiomyocytes, and its expression level is positively correlated with the degree of cardiomyocyte damage. By inhibiting the expression or activity of MITF, sorafenib-induced cardiomyocyte hypertrophy and damage can be significantly reversed. This invention provides a novel specific intervention target for the prevention and treatment of sorafenib cardiotoxicity, and has significant scientific and clinical translational value.

The invention relates to the technical field of biological diagnosis and biological medicine, in particular to application of a biomarker in prediction of sensitivity of a liver cancer patient to a sorafenib drug. The invention provides a biomarker which comprises CSNK1G3 and XPO1, and the problems that the prediction efficiency of a single marker is insufficient and the marker is disjointed with a drug resistance mechanism can be solved through joint detection. The biomarker combination is high in prediction accuracy, has clear biological mechanism support, and is easy for clinical detection. The biomarker combination provided by the invention is applied clinically, and can realize early and accurate prediction of sorafenib primary or acquired drug resistance of hepatocellular carcinoma patients, thereby guiding individualized administration and avoiding invalid treatment.

The application discloses application of a pharmaceutical composition with GL-V9 and a chemotherapeutic drug as active ingredients in treatment of tumors, and the GL-V9 can obviously achieve a drug synergistic effect when the GL-V9 is combined with a classical chemotherapeutic drug to treat tumors, and the effect is obviously superior to combination of similar drugs and the chemotherapeutic drug. The chemotherapeutic drugs include PARP1 inhibitors, capecitabine, irinotecan, sorafenib, cisplatin or 5-fluorouracil; and the tumor types include leukemia, colorectal cancer and lung cancer.

The invention belongs to the technical field of extraction of active ingredients, and provides a preparation method of a natural flavanone compound and application of the natural flavanone compound in preparation of anti-liver cancer drugs, and the application is that a sophora alopecuroide rhizome extraction mixture and a monomer are applied to preparation of anti-liver cancer drugs. According to the method, the HSCCC linear elution technology is utilized, a large number of high-purity fractions of active flavanone compound components are rapidly, efficiently and simultaneously separated from a large number of sophora alopecuroide rhizome crude extracts, and the effect of a mixture and a monomer in the sophora alopecuroide rhizome extracts combined with sorafenib on liver cancer cells MHCC97H is evaluated; the result shows that the mixture of the two flavanone compounds Alopecurone A and Alopecurone B of which the total purity is greater than 90% can be obtained by the preparation method disclosed by the invention, and the mixture and the monomer substances thereof have a growth inhibition effect on hepatoma carcinoma cells MHCC97H.

The present disclosure relates to a method of treating hepatocellular carcinoma in a human subject comprising administering an anti-Claudin-1 antibody to a human subject, wherein the hepatocellular carcinoma is resistant to sorafenib and / or PD-1 antagonists.

The invention provides a pharmaceutical composition for treating cancers. The pharmaceutical composition comprises an elephantopus scaber ethanol extract and sorafenib. Compared with the prior art, the Elephantopus scaber ethanol extract and the sorafenib combination have significant anticancer activity and synergistic effect, can treat cancers more effectively, and reduce toxic and side effects at the same time.

The present invention relates to a pharmaceutical composition for preventing or treating cancers, which contains 2, 6-dichloro-4 - (4 - (4-hydroxycyclohexylamino) -7H - pynolo [2, 3-D] pyrimidin-5-yl) phenol as an active ingredient.SOLUTION: The present invention inhibits the formation of mammospheres in breast cancer cell lines, and when compared with the anticancer drugs sorafenib and etoposide, which are widely used topoisomerase inhibitors in lung cancer, ovarian cancer, colon cancer, melanoma and the like, it has been found to exhibit an effect more marked than or equal to the anticancer drugs sorafenib and etoposide. In addition, the compound of Example 1, according to the present invention, exhibits synergistic anticancer effects when combined with radiotherapy or other anticancer drugs in breast cancer cell lines and liver cancer cell lines, and thus can be developed as an anticancer drug or food exhibiting excellent effects in the treatment of cancer.SELECTED DRAWING: Figure 12

Compositions containing cannabinoids and kinase inhibitors are useful for the treatment of hepatocellular carcinoma (HCC). Compositions containing cannabinolic acid (CBNA) and sorafenib act synergistically on HepG2 cells, an in vitro liver cancer model, and on ex vivo patient-derived xenograft (PDX) HCC models. The effects of all of the disclosed compositions are superior to sorafenib alone, which is the first- and second-line chemotherapeutic agent for the treatment of HCC.

The invention discloses a preparation method of sorafenib tosylate, which comprises the following steps: reacting a compound II with N, N '-carbonyldiimidazole to generate a compound IV, condensing the compound IV with a compound III to obtain a sorafenib (compound V) crude product, and decoloring and purifying the sorafenib crude product with activated carbon by using DMF (Dimethyl Formamide) as a refining solvent to obtain the sorafenib tosylate. And then acidifying and crystallizing to obtain the high-purity sorafenib. According to the process, amide ester impurities (such as sorafenib ethyl ester) generated when alcohol solvents such as ethanol are used are fundamentally avoided. And salifying the purified sorafenib with p-toluenesulfonic acid, and pulping with isopropanol to obtain a final product. The method is safe in process and simple and convenient to operate, the purity of the prepared sorafenib tosylate is not lower than 99.94%, no specific amide ester impurity exists, the product quality is remarkably superior to that of the prior art, and the method is suitable for industrial production.

The invention discloses FOXK2-K300 milk acylation modified polypeptide, the amino acid sequence of the FOXK2-K300 milk acylation modified polypeptide is PYYRTADKGWQNSIC, and K is modified by milk acyl; the polyclonal antibody generated by immunizing the polypeptide can specifically recognize FOXK2 lactoacylation modification, and the FOXK2 lactoacylation modification level is related to sorafenib treatment insensitivity and poor prognosis of a hepatocellular carcinoma (HCC) patient, so that the antibody can be used for preparing a reagent for predicting HCC sorafenib treatment reactivity, personalized treatment of HCC advanced patients is facilitated, and the application prospect is wide. The kit has the advantages of convenient detection, low cost, good clinical application prospect and the like.

The invention provides a nano vaccine for synergistically activating an STING pathway and dual cell death as well as a preparation method and application of the nano vaccine. The nano vaccine comprises a nano particle core (SRF (at) FeShik) formed by self-assembly of Fe < 3 + >, alkannin and sorafenib (SRF), an STING agonist cGAMP is entrapped in the nano particle core, and a composite nano structure SRF (at) FeShik-cGAMP / HA is formed through modification of low-molecular-weight hyaluronic acid (HA). The vaccine can specifically target a CD44 high-expression tumor site through HA, responsively release SRF, Fe < 2 + >, shikonin and cGAMP in a tumor cell high glutathione environment, respectively induce dual ferroptosis and necrotic apoptosis, significantly stimulate immunogen cell death (ICD), cooperatively activate an STING-TBK1-IRF3 signal channel, initiate I-type interferon expression, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, inhibit apoptosis, and inhibit the dendritic cell maturation and T cell mediated immune response are enhanced. Animal experiments prove that the nano vaccine has good targeting property, biological safety and remarkable anti-tumor efficacy, and complete regression and long-term immune memory of tumors can be realized. The invention has a wide application prospect in the field of tumor immunotherapy.

The invention provides application of combined use of amphotericin B and sorafenib in preparation of a medicine for treating liver cancer. The invention also provides a pharmaceutical composition for treating liver cancer. The pharmaceutical composition is prepared from the following raw material medicines in parts by mass: 1-3 parts of amphotericin B and 1-10 parts of sorafenib. Pharmacodynamic tests prove that the amphotericin B and the sorafenib are combined to be used for treating the liver cancer, and the synergistic interaction effect is achieved.

The present application relates to a kind of anti-tumor nanomaterial complex, it includes the SP94-PEG modified graphite alkyne carrier and antitumor drug, the SP94-PEG is multi-arm polyethylene glycol connection targeted peptide SP94, the antitumor drug includes sorafenib, siRNA and doxorubicin and ferrous ion complex, the siRNA is the nucleotide sequence of targeting SLC7A11 gene.The drug-loaded graphite alkyne nanocomposite of the present application has special advantage and good dispersibility, solves the toxic side effect and drug resistance problem brought by traditional chemotherapy drug, it belongs to the nanomedicine of cancer cell by ferroptosis targeted, can make in vitro and in vivo antitumor treatment efficiency significantly improve, is a kind of promising tumor targeted therapy strategy.

The invention belongs to the technical field of basic medicine scientific research, and particularly relates to a method for rapidly constructing a mouse atherosclerosis model by using sorafenib. According to the method, the original molding period of 12 weeks or longer is shortened to 8 weeks, and the problem of long molding time is successfully solved; in addition, the atherosclerosis mouse model constructed by the method has a very remarkable atherosclerosis effect (the blood fat levels TC, TG and HDL-C are higher); the atherosclerotic aorta plaque area is larger, the blood vessel stenosis is more serious, and foam cells in the aortic valve are increased.

The application discloses a kind of screening and anti-myeloma application of targeting c-Maf small molecule inhibitor, especially provide the application of sorafenib or glimepiride in preparation anti-myeloma drug.Aspect.The application discloses a kind of method for screening targeting c-Maf small molecule inhibitor, it includes the steps based on molecular virtual screening docking.It is found that potential compound glimepiride and sorafenib can inhibit the activity of c-Maf by the method of the application through virtual screening, molecular dynamics (MD) simulation, molecular mechanics and MM / GBSA free energy calculation and experimental analysis, both can induce the cycle stagnation and cell apoptosis of myeloma cell.The method of the application can screen more targeting c-Maf small molecule inhibitor, it is also helpful to further structure optimization based on sorafenib and glimepiride in the future, and design c-Maf small molecule inhibitor with better activity.

The application belongs to the field of proteomics research, and discloses application of a reagent in preparation of a product for detecting or treating IgG4-RD. Six PD-L1 related DEPs (RPS6KB1, NFATC1, CD3E, PTEN, PTPN6 and JAK2 proteins) can be used as biomarkers for patient stratification and identification of individuals with high risk of severe disease progression or fibrosis sequelae, secondly, activation of the PD-1 / PD-L1 pathway suggests that immune checkpoint regulation may be a new treatment method for IgG4-RD, thirdly, significant enrichment of metabolic pathways indicates that IgG4-RD is a metabolic disorder disease, which provides a way for targeted immunometabolism. Finally, drug repositioning research highlights resveratrol and sorafenib as candidate therapeutic drugs, and the potential combination of these drugs provides a new method for rebalancing immune activation and inhibition in IgG4-RD.

This invention discloses a pharmaceutical composition for alleviating sotorasidib-induced intestinal injury and its uses, belonging to the field of pharmaceutical technology. This invention proposes an intervention strategy to prevent and / or alleviate sotorasidib-induced intestinal injury by activating the cAMP signaling pathway. The cAMP signaling pathway activator can restore PKA activity and / or CREB phosphorylation levels, reduce sotorasidib-induced intestinal epithelial cell apoptosis, improve cell proliferation, and alleviate intestinal barrier damage. This invention also provides a combination of the cAMP signaling pathway activator and sotorasidib for the preparation of antitumor drugs. Cell model verification showed that the combined strategy did not significantly weaken the antitumor effect of sotorasidib, suggesting that this combined strategy has the potential for application as an adjuvant protective measure.

The present application relates to the field of nanobiomaterials, in particular to a drug-loaded nanovaccine and a preparation method and application thereof, so as to improve tumor treatment effect and biological safety. The drug-loaded nanovaccine comprises MIL-100(Fe) and a manganese-doped mesoporous silica carrier, the MIL-100(Fe) is coated on the outer surface of the manganese-doped mesoporous silica carrier, and the manganese-doped mesoporous silica carrier is loaded with sorafenib. The MF@SOR nanovaccine of the present application has very high biological safety. Meanwhile, the carrier of the present application is wrapped with a layer of MIL-100(Fe), the coating is very uniform and stable, which can further improve the bioavailability of sorafenib, maximize the use of drugs and reduce the toxic and side effects of drugs. In addition, the MF@SOR nanovaccine can also induce the body to produce immune memory, inhibit the recurrence and metastasis of tumors, the recurrence and metastasis of tumors are significantly reduced, and the treatment effect of tumors is significantly improved.

The invention provides a pharmaceutical composition for treating cancers. The pharmaceutical composition comprises abutilon tamarinense lactone and sorafenib. Compared with the prior art, the cholangiolide and the combination of cholangiolide and sorafenib have remarkable anti-cancer activity and synergistic effect, cancer can be more effectively treated, and meanwhile toxic and side effects are reduced.

The application provides application of sorafenib in preparation of a product for inhibiting Neisseria gonorrhoeae, and relates to the technical field of biology and bacteriostasis. The application comprises application of sorafenib or a derivative thereof in (I) preparation of a Neisseria gonorrhoeae inhibitor; or (II) preparation of a medicine for preventing, relieving and / or treating Neisseria gonorrhoeae; a medicine for treating or preventing infection and / or complications caused by Neisseria gonorrhoeae; a method for inhibiting or preventing growth of Neisseria gonorrhoeae; and the application provides a new potential medicine selection for treating drug-resistant gonorrhea, and has important clinical application value.

The invention discloses application of ELK1 and LINC00839 genes in regulation and control of the treatment effect of a nasopharyngeal carcinoma ferroptosis inducer, and belongs to the technical field of gene engineering. The invention discloses a key effect of the ELK1 gene and the LINC00839 gene in regulating and controlling the ferroptosis sensitivity of nasopharyngeal carcinoma cells. Experiments prove that by inhibiting the expression of ELK1 or LINC00839, the sensitivity of nasopharyngeal carcinoma cells to sorafenib, Erastatin, RSL3 and other ferroptosis inducers can be remarkably improved; on the contrary, overexpression of ELK1 or LINC00839 can significantly reduce the sensitivity of nasopharynx cancer cells to ferroptosis. The invention provides a clear target spot and technical support for developing medicines for overcoming ferroptosis resistance and enhancing nasopharyngeal carcinoma treatment effect, and provides a new solution for solving the problem of treatment failure caused by ferroptosis resistance in nasopharyngeal carcinoma.

The invention relates to the technical field of tumor treatment, in particular to a VEGFR-2 / BRD4 double-target inhibitor and application thereof. The structural general formula of the VEGFR-2 / BRD4 double-target inhibitor is as shown in a formula I in the specification. The tetrahydropteridine compound containing the aryl amide or aryl urea structure, disclosed by the invention, has relatively strong inhibitory activity on VEGFR-2 / BRD4 activity; according to the present invention, the VEGFR-2 / BRD4 double-target inhibitor has good anti-proliferative activity on tumor cells, the compound I-5 shows the optimal activity, and the activity is far superior to the positive control Sorafenib, ReGrafenib and JQ-1, the effect of the ReGrafenib and the effect of the combination of the Sorafenib and the JQ-1 respectively, and the target treatment drug for leukemia, gastrointestinal stromal tumor, liver cancer, kidney cancer, thyroid cancer, non-small cell lung cancer, colorectal cancer and the like can be prepared, and the compound I-5 can be used for the preparation of the target treatment drug for treating leukemia, gastrointestinal stromal tumor, liver cancer, kidney cancer, thyroid cancer, non-small cell lung cancer, colorectal cancer and the like.

The invention belongs to the field of tumor nano immunotherapy, and particularly relates to an iron-based photodynamic-chemical kinetics synergistic immune nano preparation for breast cancer treatment and a preparation method of the iron-based photodynamic-chemical kinetics synergistic immune nano preparation. The effective component of the nano preparation is the nano particles CyBT-Fe with good endoplasmic reticulum targeting stability, and through in-vitro and in-vivo experiments, the combination of CyBT-Fe and sorafenib (SRF) shows a huge potential of a breast cancer treatment effect. The nanoparticle CyBT-Fe is prepared from CyBT and Fe-Mil according to the mass ratio of 1: 100, and the structure of the CyBT is shown in the specification.