35 results about "Anthracycline" patented technology

The invention relates to the technical field of medicine, in particular to application of parishin E in preparation of medicine for preventing and / or treating mitochondrial dysfunction heart failure, and the heart failure particularly refers to chronic heart failure induced by anthracycline antitumor drugs and related to mitochondrial dysfunction. In-vitro experiments prove that the parishin E can remarkably improve the mitochondrial function of myocardial cells damaged by adriamycin and improve basic respiration, ATP (adenosine triphosphate) synthesis and maximum respiration capacity of the myocardial cells. In an animal model, the parishin E effectively improves heart function indexes and relieves pathological injuries such as myocardial fiber arrangement disorder and cavity enlargement. The invention provides a natural small molecule which is novel in mechanism and has development potential for clinically preventing and treating anthracycline cardiotoxicity.

The invention belongs to the technical field of medicines, and provides application of fritillaria alkaloid in preparation of a medicine for treating cardiomyopathy induced by chemotherapeutic drugs. The fritillaria alkaloid is fritillaria pallidiflora alkaloid; the chemotherapeutic drug is an anthracycline chemotherapeutic drug; the anthracycline chemotherapeutic drug is adriamycin. The fritillaria pallidiflora alkaloid can prevent and / or treat doxorubicin-induced cardiomyopathy by resisting myocardial fibrosis and relieving myocardial damage. The fritillaria pallidiflora alkaloid is a natural fritillaria pallidiflora alkaloid, through a multi-target action mechanism, cardiac function decline and cardiomyopathy damage caused by adriamycin are effectively relieved, and a novel candidate drug with potential and a treatment strategy are provided for preventing or treating chemotherapy drug induced cardiomyopathy.

The invention belongs to the technical field of biological medicines, and particularly relates to application of przewatanshinone A in preparation of a medicine for treating anti-tumor medicine cardiotoxicity. The traditional Chinese medicine-induced cardiotoxicity disclosed by the invention is cardiotoxicity caused by anthracycline drugs. Experiments prove that przewatanshinone A has a multi-target synergistic effect and can remarkably inhibit myocardial cell oxidative stress, relieve inflammatory response and protect myocardial cell functions, so that cardiotoxicity caused by anthracycline drugs is effectively prevented and treated, and a brand-new solution is provided for clinical prevention and treatment of cardiotoxicity caused by anthracycline drugs.

The invention provides a method of characterising a DNA sample obtained from a tumour, the method including the steps of: determining the presence or absence of a plurality of base substitution signatures, rearrangement signatures and indel signatures in the sample and copy number profiles for the sample; generating, from the presence or absence of said plurality of base substitution signatures, rearrangement signatures and indel signatures and the copy number profile for the sample, a probabilistic score; and based on said probabilistic score, identifying whether said sample has a high or low likelihood of being homologous recombination (HR)-deficient. Identification of a tumour as HR-deficient may be used to inform treatment choices, for example treatment with a PARP inhibitor or platinum therapy or an anthracycline.

The invention discloses a class of fluorobenzoyl anthracycline derivatives, and preparation method for preparing and applications of the same. The fluorobenzoyl anthracycline derivatives have chemical formula ofwhere R1 is selected from the group consisting of —CH3, —CH2OH and —O—CH3 groups; R2 is selected from the group consisting of —H, —OH and —O—CH3 groups; and R3 is a trifluoromethyl-substituted benzoyl group or a trifluoromethylphenyl-substituted benzoyl group. The preparation method involves the derivatization of fluorobenzoyl groups on the amino group of anthracycline derivatives. These derivatives act as ablation media for chemical ablation of heterogeneous myocardial tissues, achieving effective myocardial damage with targeted localization and controllable damage characteristics.

The present invention concerns antibody-conjugate having general structure (2):wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

IT-139, sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)], is an intravenously administered small molecule compound. In preclinical anti-tumor and mechanism of action studies, IT-139 showed activity against a broad range of tumor types, including those which are resistant to standard anti-cancer agents (e.g., platinums, vinca alkaloids, taxanes, anthracyclines). This activity is believed to arise from IT-139's novel mechanism of action that targets the GRP78 pathway. It was found that up-regulation of GRP78 is a key cancer cell survival pathway. Downregulation of GRP78 using IT-139 removes this resistance pathway allowing for chemotherapy and immuno-oncology agents to be more effective in treating cancer.

The present invention provides anthracycline-linker reagents for the preparation of therapeutic antibody-drug conjugate (ADC) compounds. The present invention also provides therapeutic antibody-drug conjugate (ADC) compounds comprising anthracycline drug moieties, with biological activity against cancer cells. The compounds may inhibit tumor growth in mammals and may be useful for treating human cancer patients. Aspects of the invention include methods of making, methods of preparing, methods of synthesis, methods of conjugation, and methods of purification of the anthracycline-linker reagents and of the antibody-drug conjugate compounds.

The present invention provides a combination of therapeutic agents for preventing and / or treating neoplastic diseases. Specifically, the present invention provides an antibody-drug conjugate in combination with VEGFR TKI and / or in combination with anthracycline in the preparation of a drug for preventing and / or treating cancer.

The application provides a cytochrome P450 enzyme DoxA (CYP129 subfamily), and the amino acid sequence of the cytochrome P450 enzyme DoxA is SEQ ID NO:1. The application also provides a use of the cytochrome P450 enzyme DoxA, which is catalyzing synthesis of 13-dihydrodaunorubicin or 13-dihydrodaunorubicin derivatives from anthracycline compound 13-deoxydaunorubicin; and the method, wherein the cytochrome P450 enzyme DoxA catalyzes 13-deoxydaunorubicin by using NAD(P)H. The application provides a cytochrome P450 enzyme DoxA which can directly use NAD(P)H, can synthesize 13-dihydrodaunorubicin by using NAD(P)H in one step, does not need to use electron transfer protein for assistance, simplifies a reaction system, reduces reaction cost, enhances controllability and stability of the reaction, and the electron transfer process is more direct and efficient, and the catalytic efficiency of the reaction is improved.

This invention is directed to compositions comprising bisantrene, particularly formulations of bisantrene dihydrochloride, wherein the formulations are suitable for intravenous administration into peripheral veins as well as methods for their use and methods for preparation of such compositions. The compositions according to the present invention eliminate the need to administer bisantrene by central venous catheter administration. The compositions can be used to treat malignancies and other conditions, and may be used for cardioprotection in patients undergoing chemotherapy with anthracycline-based anti-neoplastic agents. The inclusion of α-hydroxy acids in compositions according to the present invention improves the stability of such compositions and prevents precipitation of the bisantrene.

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 15 to 25 parts of radix salviae miltiorrhizae and 15 to 25 parts of radix ginseng rubra according to a weight ratio of 1 to 1. Based on the traditional Chinese medicine theory of tonifying qi, activating blood, detoxifying and dredging collaterals, the traditional Chinese medicine composition is provided for the first time to inhibit neutrophil extracellular traps (NETosis) and inflammatory response in a targeted manner, so as to prevent and treat cardiotoxicity caused by anthracycline drugs. Animal experiments show that the traditional Chinese medicine composition can remarkably improve the heart function, relieve myocardial damage and inhibit release of inflammatory factors, and has good safety. Clinical cases prove that the traditional Chinese medicine can effectively relieve symptoms of patients and guarantee smooth chemotherapy. The invention provides a brand-new, effective and safe traditional Chinese medicine treatment scheme for preventing and treating anthracycline cardiotoxicity.

This invention relates to the field of biomedical technology, and in particular to the application of hD1R protein in the preparation of drugs for the treatment of AML. Addressing the current lack of systematic and in-depth research on whether hD1R protein can directly act on AML cells and whether it has a synergistic effect with existing standard chemotherapy drugs (such as anthracyclines), this invention, through a series of in vivo and in vitro experiments and the construction of a NOD / SCID mouse transplantation model, confirms that hD1R protein alone can effectively inhibit AML cell proliferation, induce apoptosis, inhibit AML cell colony formation, and downregulate the expression of the key anti-apoptotic gene Bcl2 in AML cells. It also confirms that hD1R treatment can significantly prolong the survival of model mice. Furthermore, by setting up a Dox+hD1R group (combined experimental group), it is confirmed that when hD1R protein is used in combination with anthracycline chemotherapy drugs, it exhibits significant synergistic effects in inhibiting AML cell proliferation, promoting AML cell apoptosis, downregulating the expression of the anti-apoptotic gene Bcl2 in AML cells, and inhibiting AML cell colony formation.

The present disclosure is directed to novel PNU Anthracycline Derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined in the above disclosure. The disclosure is also directed to pharmaceutical compositions comprising the PNU Anthracycline Derivatives, and the use of these compounds and compositions in the prevention or treatment of cellular proliferative disorders.

The present disclosure generally relates to technologies for treating cancer, including brain cancers such as a glioblastoma, methods of increasing the concentration of anthracy clines and immune checkpoint modulators in the brain of a subject, and methods of improving use of immune checkpoint modulators in brain cancers. Also disclosed herein are compositions and methods for treating a brain tumor.

The invention belongs to the technical field of biological medicines, and discloses a new medical application of an hERG / Kv11.1 channel activator NS-1643, so that new application of old medicines is realized. The NS-1643 is traditionally used for anti-arrhythmia research and development, it is found for the first time that NS-1643 can effectively treat cardiotoxicity induced by anthracycline drugs (such as doxorubicin), and meanwhile NS-1643 can be used for preventing or treating ferroptosis-related cardiovascular diseases such as myocardial ischemia reperfusion injury, myocardial infarction and heart failure. The invention further provides a pharmaceutical composition containing the NS-1643, the NS-1643 or pharmaceutical salt, ester, solvate and the like of the NS-1643 are taken as active ingredients of the composition, and the active ingredients are matched with auxiliary ingredients acceptable in biological pharmacy, so that the composition can be prepared into sterile dosage forms such as injections, oral preparations and the like, and the process is stable and controllable. Cell experiments prove that NS-1643 has a remarkable protective effect on ferroptosis-induced myocardial cell injury (EC50 is approximately equal to 2.7 mu M); animal experiments prove that the doxorubicin-induced mouse death risk can be completely reversed, the heart function is remarkably improved, and myocardial fibrosis and lipid peroxidation damage are relieved. The application expands the clinical application range of NS-1643, has the advantages of high clinical transformation potential, clear treatment effect and the like, provides a new effective strategy for prevention and treatment of anthracycline cardiotoxicity and related cardiovascular diseases, and has important clinical application value and industrial transformation prospect.

A method of preparing a water-soluble complex comprising an anthracycline or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal or polymorph thereof, by mixing the anthracycline with a non-nutritive sugar and / or a surfactant in the presence of a solvent, removing the solvent and dissolving the water-soluble complex in water. Also described are the water-soluble complex and compositions comprising the complex.

[Problem] To provide a safe prophylactic agent or therapeutic agent for side effects of an anthracycline anticancer agent, the agent having a broad range of applications. [Solution] In a treatment of a cancer using an anthracycline anticancer agent, 5-aminolevulinic acid is used in combination.

The invention discloses an Au-coated Ag / C-CNF / PEGDA hydrogel SERS (Surface Enhanced Raman Scattering) sensor as well as a preparation method and application thereof, and belongs to the technical field of analysis and detection. Gold and silver nanoparticles with a core-shell structure, polyethylene glycol diacrylate and carboxylated cellulose react to form an Au-coated Ag / C-CNF / PEGDA hydrogel prepolymer solution, and the hydrogel prepolymer solution is subjected to ultraviolet crosslinking under the action of a photoinitiator to form the porous three-dimensional network structure Au-coated Ag / C-CNF / PEGDA hydrogel SERS sensor with a synergistic effect. The hydrogel sensor provided by the invention not only can accurately detect 10 <-9 > M-10 <-5 > M Raman signal molecule rhodamine 6G (R6G), but also has good sensitivity and excellent uniformity, the RSD is as low as 4.92%, and the detection limits on anthracycline antitumor drugs doxorubicin (DOX) and mitoxantrone (MTO) respectively reach 3.4 * 10 <-8 > M and 3.6 * 10 <-9 > M.

Disclosed herein are DNA origami nanostmcture that can be functionalized for personalized and targeted drug delivery. The disclosed nanostructures enter cells through the endolysosomal pathway and circumvent drug resistance mechanisms in target cells. The disclosed nanostructures can be loaded small molecule drugs (e.g. anthracyclines, anti-metabolites) and nucleic acids (e.g. antisense oligonucleotides, siRNA, miRNA) with targeting and / or therapeutic antibodies against tumor-specific antigens (e.g. anti-CD33, anti-CD20) that can be modified to treat to a wide range of cancers and ultimately tailored to specific patients' needs for precision medicine.

The present application relates to the field of biological medicine, and discloses application of polysaccharide of smilax sieboldi and anthracycline compound in preparation of triple-negative breast cancer treatment drugs. First, the present application first discovers that the polysaccharide of smilax sieboldi is a cell ferroptosis inducer. Secondly, the present application first discovers that the polysaccharide of smilax sieboldi and the anthracycline compound can play a synergistic and attenuating role in the treatment of triple-negative breast cancer, greatly reduce the toxic and side effects of the anthracycline compound, so as to improve the prognosis and survival quality of the triple-negative breast cancer patients, and improve the survival rate of the patients.

The present disclosure relates to novel PNU anthracycline derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 is as defined in this disclosure. The disclosure also relates to pharmaceutical compositions comprising PNU anthracycline derivatives and the use of these compounds and compositions in the prevention or treatment of cell proliferative disorders. [Formula 1] TIFF2026500987000090.tif46153

The present disclosure relates to linker-payloads comprising the structure of Formula (I), and pharmaceutically acceptable salts, solvates, or stereoisomers thereof. The present disclosure also relates to pharmaceutical compositions comprising these compounds, and the use of these compounds, their intermediates, and compositions in the prevention or treatment of cancer and / or tumors. [Formula 1] TIFF2025542248000197.tif76165

The application discloses a tumor microenvironment responsive nano-composite hydrogel co-drug delivery system and a preparation method thereof, and belongs to the field of antitumor materials. The nano-composite hydrogel co-drug delivery system is a sodium alginate hydrogel with hyaluronic acid encapsulated drug-loaded nanoparticles embedded in the interior. The drug-loaded nanoparticles encapsulate anthracycline chemotherapy drugs and tyrosine kinase inhibitors; the anthracycline chemotherapy drugs are connected to the hyaluronic acid side chain through a hydrazone bond to form a polymer prodrug, and the tyrosine kinase inhibitors are encapsulated into the hydrophobic core of the nanoparticles through self-assembly of the polymer prodrug molecules to obtain the hyaluronic acid encapsulated drug-loaded nanoparticles. The sodium alginate hydrogel is a dopamine modified sodium alginate hydrogel. The nano-composite hydrogel co-drug delivery system is easy to be injected intratumorally and paratumorally, can be slowly degraded in the body, and can target and synchronously deliver the drugs to tumor cells by using the escaped nanoparticles, so as to inhibit tumor cell proliferation, invasion and migration, and realize a synergistic antitumor effect.

This invention provides an Auger electron radiotherapy drug that can selectively and effectively release a sufficient amount of Auger electrons into the nuclear DNA of cancer cells, even in small amounts, thereby reducing or killing cancer cells. The Auger electron radioactive isotope has a half-life that is not too short but not too long, making it highly safe and readily available. [Solution] The Auger electron radioactive therapeutic agent is encapsulated in a stimulus-responsive liposome that accumulates in cancer tissue and / or cancer cells, such that an anthracycline derivative is released upon stimulation, in which an Auger electron-emitting radioisotope-substituted benzene ring-containing group or radioisotope-substituted alkyl group is covalently bonded to the keto or amino group of anthracyclines selected from doxorubicin or daunorubicin and their reduced forms or alkoxy group-substituted forms thereof, is a stimulus-responsive liposome, or is bound to an antibody, oligopeptide, or antigen that accumulates in cancer tissue and / or cancer cells via a stimulus-responsive linker.

The invention provides a method for synthesizing anthracycline compounds for treating chronic myelogenous leukemia by an enzyme method. The two anthracycline compounds are 10-decarboxyl-13-deoxyerythromycin and 10-hydroxy-13-deoxyerythromycin. The invention further provides a preparation method of the anthracycline compounds for treating the chronic myelogenous leukemia. The invention discovers and verifies that the 10-decarboxyl-13-deoxyerythromycin and the 10-hydroxy-13-deoxyerythromycin have obvious activity of resisting human chronic myeloid leukemia cells for the first time. And compared with adriamycin, the inhibition activity is improved by about 15 and 20 times. Therefore, the compound has the outstanding potential of being developed into an efficient new-generation anthracycline anti-tumor drug, and provides a new candidate drug choice for leukemia treatment.

The present application relates to the application of VPS34 inhibitor in the preparation of the drug for preventing and treating anthracycline-induced cardiotoxicity. The present application creatively finds that VPS34 inhibitor represented by SAR405 has obvious prevention and treatment effect on anthracycline-induced cardiotoxicity (AIC), and the present application verifies the role of autophagy in AIC mouse model based on cardiomyocyte strain and gene knockout mouse as the research object, and proves that early inhibition of autophagy by Atg7 gene knockout can reduce AIC, and VPS34 inhibitor can inhibit Vps34 kinase activity by interacting with the ATP binding domain of Vps34, thereby interfering with the occurrence of autophagy, which provides a new strategy for preventing and treating anthracycline-induced cardiotoxicity (AIC).

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of an anthracene ring medicine intermediate. The anthracene ring medicine intermediate is prepared by reacting SM with butanone glycol ketal, compared with the prior art, the preparation method can quantitatively obtain the related intermediate at room temperature, can significantly reduce the reaction temperature and the use of water separator, can simplify the reaction operation, can reduce the energy consumption, can significantly improve the yield and purity of the product, and is more suitable for industrial application.

Disclosed are anti-TROP2 antibody-drug conjugates comprising a derivative of the anthracycline metabolite PNU-159682 conjugated to an antibody that preferentially binds cells that express TROP2 more than cells that express TROP2 less.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).