106 results about "Sorafenib" patented technology

The invention relates to the field of biological medicine, in particular to IMSFs hydrogel, a ferroptosis induction system, a preparation method and application. The IMSFs hydrogel comprises a hydrogel body, and ferroferric oxide nanoparticles and sorafenib are loaded in the hydrogel body in a wrapping manner. The IMSFs hydrogel can be used as an injectable cascade ferroptosis anti-cancer drug. The preparation method of the IMSFs hydrogel comprises the following steps: firstly, preparing a silk fibroin-hyaluronic acid hydrogel body: dissolving silk hydrogel and hyaluronic acid in a lithium bromide solution; bDDE is added into the dissolved solution, and incubation is carried out; then dialyzing and washing with deionized water to obtain a silk fibroin-hyaluronic acid hydrogel body; and then loading the sorafenib nanoparticles and the ferroferric oxide nanoparticles into the silk fibroin-hyaluronic acid hydrogel body. The IMSFs hydrogel disclosed by the invention integrates magnetic thermal response and drug controlled release, and can be injected to a tumor site, so that the treatment effect on TNBC is remarkably improved.

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 a sulfatase-driven polypeptide condensate with a chemotherapy sensitization effect and a preparation method thereof, and belongs to the field of biological medicines. According to the principle that sulfatase can catalyze hydrolysis of sulfate bonds, main polypeptide YSO4F responded by sulfatase enzyme is designed and synthesized; and the enzyme response aggregate m-YSO4F-LSG is blended with a protein G3BP2 ligand FGDF-YSO4F to prepare the enzyme response aggregate m-YSO4F-LSG with a sorafenib chemosensitization effect. Tumor cells can generate stress particles with a chemotherapy drug resistance effect under the stimulation of a chemotherapy drug sorafenib, the treatment effect of the sorafenib is weakened, and the protein G3BP2 is one of core proteins of the stress particles. After the m-YSO4F-LSG enters tumor cells, sulfate groups are hydrolyzed under the catalytic action of sulfatase overexpressed in tumor cell lysosomes, so that phase separation liquid drops d-YF-LSG with high affinity to protein G3BP2 are formed in the cells in situ, the phase separation liquid drops d-YF-LSG act with the protein G3BP2 and are fused with stress particles, chemotherapy drug resistance generated by the stress particles is inhibited, and the chemotherapy effect is improved. The treatment effect is improved.

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 an NIR-II emitted J aggregation-induced emission photosensitizer, a pharmaceutical composition constructed by the photosensitizer, a preparation method and application of the photosensitizer. The photosensitizer can generate cytotoxic I-type active oxygen under illumination, and has excellent NIR-II region fluorescence imaging capability and phototherapy performance. The photosensitizer is further assembled with sorafenib to form a pharmaceutical composition, and the pharmaceutical composition has a J aggregation-induced secondary self-assembly characteristic, realizes long-time imaging at a tumor site, exerts dual functions of NIR-II region fluorescence imaging and tumor treatment, and is good in stability, low in toxic and side effects and wide in clinical application prospect. # imgabs0 #

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 provides a pharmaceutical composition for treating MSS intestinal cancer, and belongs to the technical field of biological medicine, the pharmaceutical composition is used for deeply researching a treatment scheme for effectively inhibiting the MSS intestinal cancer, carrying out basic research from protein purification, proteomics, siRNA libraries and the like, and trying to develop a brand new treatment scheme and a treatment mode using nitixinone, sorafenib and PD1 antibodies; the three medicines are combined for use, so that a remarkable synergistic effect is achieved, and the tumor is successfully changed from cold to hot. The pharmaceutical composition provided by the invention has an important clinical value, breaks through the current difficulty in treatment of MSS intestinal cancer, and opens a brand new direction of application of immunotherapy in clinical advanced metastatic colorectal cancer.

The invention belongs to the field of biological medicine, and particularly relates to a fusobacterium nucleatum FtsZ protease inhibitor and application thereof. On the basis of the idea of new use of old drugs, drugs approved by FDA are subjected to structure-based virtual screening and molecular dynamics simulation, and sorafenib, ponatinib, ceritinib and ibastine can be stably combined to active sites of fusobacterium nucleatum FtsZ protease; in-vitro experiments also show that sorafenib, ponatinib, ceritinib and ibastine are inhibitors with the fusobacterium nucleatum FtsZ protease, so that new antibacterial applications of sorafenib, ponatinib, ceritinib and ibastine are explored. The invention not only provides a new angle for antibiotic discovery, but also provides an example for rapid development of a novel FtsZ protease inhibitor.

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 relates to a drug combination of annona squamosa lactone compounds and sorafenib (SF), which is characterized in that four common human hepatoma cell lines HepG2, HuH7, MHCC97H and HCCLM3 are used as research objects, and the drug combination effect among different components is evaluated by using an MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 3-diphenyltetrazolium bromide) method and Synergy Finder software. The combination of the compound and SF shows an obvious synergistic inhibition effect on the growth of hepatoma carcinoma cells, and meanwhile, the pharmaceutical composition can synergistically reduce the ATP level of the hepatoma carcinoma cells and induce hepatoma carcinoma cell apoptosis. Pharmacodynamic experiments show that the compounds annonacin and SF can synergistically inhibit tumor growth and induce tumor cell apoptosis, and have no obvious toxicity to normal organs of nude mice at a low dosage. In addition, transcriptome analysis predicts that the anti-liver cancer target of the annonacin is possibly related to the SLC33A1 gene. The method can be used for preparing anti-hepatoma drugs and researching related mechanisms. The annona lactone compound disclosed by the invention is derived from annona montana Macf. Which is an annona plant, namely annona montana Macf.

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 present disclosure relates to a method of treating hepatocellular carcinoma in a human subject comprising administering to the human subject an anti-tight junction protein-1 antibody wherein the hepatocellular carcinoma is resistant to sorafenib and / or a PD-1 antagonist.

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: