84 results about "Sorafenib" patented technology

The present invention provides a multi-modal model construction method and system for predicting the efficacy of sorafenib in hepatocellular carcinoma. The method comprises: step 1, collecting clinical information of a target patient, and generating a whole slide image; step 2, preprocessing clinical data, and retaining clinical features as input for a multi-modal deep learning model; step 3, preprocessing the whole slide image; step 4, constructing an image model, acquiring patch-level scores of the pathological image on the basis of the preprocessed image and by using different aggregation algorithms, and predicting the score of the whole pathological image to obtain best model features; step 5, constructing a multi-modal model, performing modal fusion on the best model features and the clinical features, and outputting an image-level or patient-level prediction result; and step 6, testing and evaluating the model. The present invention achieves bimodal input of a pathological image and clinical information, fully utilizes the complementarity of the two types of modal data, and thus improves prediction accuracy.

The invention discloses an application of a pharmaceutical composition of erianin (ERI) and sorafenib (SOR) in preparation of an anti-liver cancer drug. The invention further discloses a pharmaceutical composition which comprises ERI and SOR, and the specific molar ratio of ERI to SOR is optimized and determined through an in-vitro experiment. The composition is developed based on multi-mode screening (network pharmacology prediction, molecular docking and molecular dynamics simulation) of STAT3 targets, and in-vitro experiments prove that the composition has synergistic anti-tumor activity and can be used for preparing anti-liver cancer drugs. The invention further discloses a development method of the ERI-SOR composition integrated with multi-mode computational simulation. Experiments prove that ERI and SOR both show a remarkable synergistic effect (combination index (CI) lt, 1) at the concentration of 0.5-16 [mu] M, CI at the optimal ratio (1: 1, 4 [mu] M + 4 [mu] M) reaches 0.617, the cell proliferation inhibition effect is remarkable compared with that of a single drug, and the excellent synergistic effect is shown.

The invention relates to a structure, synthesis and application of morpholine ring oligonucleotide. A morpholine ring oligonucleotide structure is named Mo-CEBPA, can induce intracellular redox imbalance and trigger ferroptosis by inhibiting expression of CEBPA in hepatoma carcinoma cells, can assist sorafenib in killing hepatoma carcinoma cells, and overcomes the defect that existing drugs cannot efficiently induce hepatoma carcinoma cell ferroptosis.

The invention discloses a sorafenib-paclitaxel combined prodrug as well as a preparation method and application thereof, and relates to the field of chemical pharmacy, a prodrug strategy is utilized, sorafenib and paclitaxel are covalently linked through a disulfide bond, and an S-PTX drug is successfully prepared. The drug can be self-assembled to form stable nanoparticles in an aqueous solution system containing 1% of absolute ethyl alcohol and 1% of polyoxyethylated castor oil by means of hydrophobic interaction, Van der Waals force and the special chemical properties of disulfide bonds. According to the invention, the drug delivery is carried out without any additional carrier, so that the problem of carrier toxicity when the carrier is introduced into the traditional nano delivery system is avoided, the safety of the drug in in-vivo application is greatly improved, and a solid and reliable foundation is provided for subsequent clinical treatment. The sorafenib-paclitaxel combined prodrug S-PTX prepared by the invention effectively solves the problem of drug resistance caused by medication of a single drug.

The invention discloses application of sorafenib in maintenance treatment of acute myelogenous leukemia after transplantation, and relates to the technical field of medicines, and the key points of the technical scheme are as follows: it is found for the first time that secretion and killing functions of NK cells can be enhanced by using sorafenib for maintenance treatment after transplantation; sorafenib enhances communication between macrophages and NK cells by promoting secretion of macrophage proinflammatory factors, so that the function of NK cells is enhanced. The invention clarifies that sorafenib enhances the GVL effect of NK cells in a low tumor load environment, discusses the molecular mechanism of sorafenib for enhancing the NK cell function by promoting macrophage metabolism reprogramming, and provides a new thought for maintaining precision and optimization of treatment after transplantation.

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 present invention discloses a tumor-activated sorafenib prodrug, its preparation method, and its application, belonging to the field of biomedicine technology. The present invention designs a tumor-activated sorafenib prodrug, composed of sorafenib and ferrocenecarboxylic acid molecules as its main structure. It can specifically activate cytotoxicity at the tumor site, and compared to sorafenib, it is more effective in killing liver cancer cells. Furthermore, it undergoes an in situ Fenton reaction, generating oxygen to alleviate tumor hypoxia and reduce tumor invasion and migration. The Fenton reaction can generate highly toxic hydroxyl radicals, which kill liver cancer cells and provide auxiliary treatment.

The invention provides a pharmaceutical composition and application thereof in preparation of medicines for treating tumors. The pharmaceutical composition comprises the orbitrazine fumarate, a second active agent and pharmaceutically acceptable auxiliary materials. The second active agent comprises at least one of tamoxifen, irinotecan hydrochloride, sorafenib, cis-platinum, doxorubicin hydrochloride, paclitaxel and etoposide. The scheme provided by the invention has a remarkable synergistic anti-tumor effect, and a combined medication scheme is expected to provide a safer and more effective treatment choice for tumor patients, so that the pharmaceutical composition has an important clinical application value.

Biomarkers are provided that predict whether a subject having a hepatocellular carcinoma is responsive to a therapy comprising sorafenib or a pharmaceutically acceptable salt thereof. The biomarkers, compositions, and methods described herein are useful in selecting appropriate treatment modalities for and treating a subject having, suspected of having, or at risk of developing a hepatocellular carcinoma.

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.

The invention discloses a targeted modified type co-drug-loading liposome and a preparation method and application thereof, and belongs to the field of pharmaceutical preparations, the drug-loading liposome comprises phospholipid, cholesterol, a targeted ligand and an anti-hepatic fibrosis drug, the targeted ligand comprises one of vitamin A, hyaluronic acid, glycyrrhetinic acid and sialic acid, and the anti-hepatic fibrosis drug comprises one of phospholipid, cholesterol and anti-hepatic fibrosis drugs. The anti-hepatic fibrosis medicine is prepared from artesunate and sorafenib. The drug-loaded liposome prepared by the invention can actively target the hepatic stellate cells through a receptor-ligand specific binding effect, so that the uptake efficiency of the hepatic stellate cells is improved. The artesunate and the sorafenib are released in cells, redox imbalance in the cells is caused by the synergistic effect of the artesunate and the sorafenib, hepatostellate cells are induced to generate ferroptosis, and therefore efficient anti-fibrosis treatment is achieved.

The invention provides a method for preparing a sorafenib-cholic acid coupling prodrug based on step-by-step coupling of sorafenib modular assembly, which comprises the following steps of: firstly synthesizing a complete sorafenib part by taking tert-butyl-(iodo-oxy) dimethylsilane as a linker, and after a sorafenib module is assembled, preparing the sorafenib-cholic acid coupling prodrug through step-by-step coupling, thereby obtaining the sorafenib-cholic acid coupling prodrug. And then coupling with cholic acid compounds step by step through deprotection. According to the method, the reaction steps are greatly reduced, the reaction can be carried out under the room temperature condition, the safety of the synthesis process is improved, especially depending on the unique connexon design and through the specific binding mechanism of the connexon and the sorafenib module, on one hand, the yield of each reaction step is remarkably improved, and on the other hand, the yield of the sorafenib module is greatly increased; the preparation efficiency of a target product is greatly improved; and on the other hand, side reaction is blocked from the reaction source, so that the purification difficulty of the product is reduced, and the controllability of the whole synthesis process is enhanced.

Described herein are methods useful for the treatment of cancers in a canine subject with a pharmaceutical compositions comprising HDAC inhibitors, Rapamycin, Dasatinib, Lapatinib, Trametinib, Vorinostat, Imatinib, Crizotinib, Sorafenib, and combinations thereof. Also described herein are methods for identification of subjects with cancers that will benefit from administration of the pharmaceutical compositions comprising HIDAC inhibitors, Rapamycin, Dasatinib, Lapatinib, Trametinib, Vorinostat, Imatinib, Crizotinib, Sorafenib, and combinations thereof. In certain aspects, the methods described herein further comprise administering a therapeutically effective amount of at least one additional anti-cancer agent.

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 detection, and particularly discloses a detection method of a bionic nano-carrier system based on a GPC3 engineering macrophage membrane in liver cancer treatment, and the detection method comprises the steps of S1, nanoparticle preparation, S2, drug encapsulation, S3, macrophage membrane MM preparation, S4, nanoparticle and macrophage membrane combination, S5, GPC3 targeted modification, and S6, in-vitro cell experimental verification. Through modification of the GPC3 targeting peptide, the nanoparticles can specifically target liver cancer cells, so that the targeting property of liver cancer treatment is greatly improved, and damage to normal tissues is reduced; the use of the macrophage membrane effectively avoids the phagocytosis of an immune system, enhances the circulation time and stability of the drug in vivo, improves the immunotherapy effect, and can significantly induce ferroptosis of liver cancer cells in combination with sorafenib (Sor) and astragaloside IV (As), thereby providing a novel treatment strategy and improving the treatment effect of liver cancer.

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 present invention discloses a microneedle patch loaded with sorafenib and copper-doped Prussian blue nanomaterials and its use in the in situ treatment of triple-negative breast cancer. The microneedle patch contains sorafenib and copper-doped Prussian blue nanomaterials within its needles. The microneedle patch can precisely deliver nanoparticles and sorafenib to tumor tissue, enhancing the chemokinetic effect through efficient and gentle photothermal therapy. The synergistic drug-induced ferroptosis of triple-negative breast cancer cells enhances ferroptosis, further inducing cell death. This provides a novel and promising treatment approach for in situ triple-negative breast cancer.

The present application relates to the field of organic electrochemistry and medical synthesis, and particularly relates to a preparation method of electrochemical synthesis of N-substituted pyridine-2-formamide. The method has the following technical advantages: no additional oxidizing agent or reducing agent is needed in the electrochemical synthesis, the environmental pollution and the reaction danger are reduced, the reaction condition is mild, the process flow is short, the reaction selectivity is good, the yield is high, and the method is environment-friendly. Specifically, in the present application, pyridine compounds and N-substituted oxamic acid are used as raw materials, and under the electrochemical reaction condition, the pyridine ring is directly activated on the carbon hydrogen to obtain N-substituted pyridine-2-formamide, wherein 4-chloro-N-methyl pyridine-2-formamide is a key intermediate of the antitumor drugs regorafenib and sorafenib, and the reaction equation is represented as:

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 application discloses a traditional Chinese medicine composition for treating renal clear cell carcinoma and a preparation method and application thereof, and belongs to the technical field of medicines. The traditional Chinese medicine composition provided by the application comprises ginseng, astragalus, atractylodes, poria cocos, herba impatiens, oldenlandia, zedoary, dogwood fruit, ligustrum lucidum and prunella vulgaris. The traditional Chinese medicine composition provided by the application is scientific and reasonable in combination, can support healthy qi and eliminate pathogenic factors, clear heat and resolve toxins, activate blood and resolve stasis, and soften and resolve hard masses. The clinical experimental results show that the traditional Chinese medicine composition provided by the application can effectively treat renal clear cell carcinoma, and the treatment efficiency is better than that of the targeted drug sorafenib; and the medicine is safe, has no obvious toxic and side effects, and performs well in improving patient's traditional Chinese medicine syndromes, improving the quality of life and reducing the level of tumor markers. The application provides a new idea and method for treating renal clear cell carcinoma, and has significant clinical significance and important popularization value.

The invention discloses a sorafenib derivative capable of regulating and controlling a PI3K-AKT pathway and inducing DNA damage as well as a preparation method and application of the sorafenib derivative, and belongs to the technical field of medicine synthesis. According to the technical scheme, the molecular structure of the sorafenib derivative is a novel-structure sorafenib derivative designed and synthesized by the invention, and the compound can induce HepG2 cell DNA damage and apoptosis, can regulate and control a PI3K-AKT pathway, has certain safety, and can be used for preparing the sorafenib derivative. The compound has the potential of becoming a potential anti-tumor lead compound.

The invention discovers the association between TM9SF4 and liver cancer for the first time, and provides application of the TM9SF4 inhibitor and the composition thereof in preparation of medicines for preventing and treating liver cancer. In-vivo and in-vitro experiments show that by inhibiting TM9SF4, migration and invasion of tumor cells can be effectively inhibited by inhibiting cell proliferation and cloning of tumors, energy metabolism of the tumors can be regulated, and particularly, liver cancer can be prevented and treated by inhibiting a glycolysis mechanism. The invention also accidentally finds that the TM9SF4 inhibitor and sorafenib have a synergistic effect on promoting apoptosis of tumor cells when being combined for use. The results show that the TM9SF4 lays a foundation for developing a novel targeted therapy strategy for liver cancer, provides a new possibility for clinical treatment, and shows a wide application prospect.

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.