20 results about "Alkylating antineoplastic agent" patented technology

The present invention provides a straightforward process for preparing pyrimido[6,1- a]isoquinoline-4-ones of formula (I), or a pharmaceutically acceptable acid addition salt thereof, preferably ensifentrine, involving the reaction of a precursor with an advanced alkylating agent.

The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

The present disclosure is directed to a method of treating glioblastoma in a subject in need thereof comprising administering to said subject an efficient amount of a radiopharmaceutical compound. The present disclosure is also directed to methods of treating glioblastoma in a subject in need thereof comprising administering to said subject an efficient amount of a radiopharmaceutical compound in combination with a step of irradiating the subject with an efficient dose of ionizing radiations, and optionally, with a therapeutically efficient amount of an alkylating agent, preferably temozolomide.

The invention belongs to the technical field of chemical synthesis, and particularly relates to an indazole alkaloid derivative as well as a preparation method and application thereof. Comprising the following steps: under an alkaline condition, carrying out alkylation reaction on a compound a and an alkylating agent to obtain a compound b; performing demethylation reaction on the compound b and a demethylation reagent to obtain a compound c; carrying out glycosylation reaction on the compound c and sugar bromide to obtain a compound d; in a sodium methoxide and solvent system, removing acetyl on glycosyl of the compound d to obtain the indazole alkaloid derivative. Or carrying out oxidation reaction on the compound d and methyl iodide to obtain an intermediate; and removing acetyl on glycosyl of the intermediate in a sodium methoxide and solvent system to obtain the indazole alkaloid derivative. The invention provides a preparation method of an indazole alkaloid derivative, which is green, simple, convenient and efficient.

The present invention relates to synergistic combinations of DNA-alkylating ADCs and ATR inhibitors.

The disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.

The present invention discloses a nitrogen mustard-synergistic strontium ion antibacterial fabric, as well as its preparation method and use. An azo drug, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide, is prepared using dopamine hydrochloride and N-phenyldiethanolamine. The drug is then coordinated with strontium ions on fabric fibers through in-situ growth to form nanoparticles. Upon contact with bacteria, the functionally coated fabric releases nitrogen mustard within the bacterial environment, forming a strong electrophilic alkylating agent within the cells. This covalently binds to electron-rich groups in DNA, RNA, and some enzymes, deactivating them and killing the bacteria. Furthermore, a large amount of strontium ions slowly released from the antibacterial fabric can be adsorbed on the surface of bacterial cell membranes, causing a voltage difference between the inside and outside of the cell membranes, weakening and rupturing the cell membranes. The strontium ions then enter the cells and hinder their formation and metabolism, thereby achieving a synergistic antibacterial effect.

This invention relates to agents, compositions, and methods for use in treating or ameliorating symptoms of cancer. Exemplary synergistic therapies include the use of antisense oligonucleotide agents for suppressing expression of TGF-β2 in combination with alkylating agents or HDAC inhibitors. Patients can be distinguished by reduced histone deacetylases. Additional therapies include the use of antisense oligonucleotide agents for suppressing expression of TGF-β2 for patients who have (a) low genomic methylation and / or (b) high TGF-β2 expression. Diagnostic information and methods are provided with histone deacetylases.

The invention relates to application of an AKT inhibitor to preparation of a medicine for preventing or treating ovarian cancer, and application of the AKT inhibitor combined with other ovarian cancer treatment medicines including one or more of a PARP inhibitor, a plant chemotherapy medicine, an antibiotic chemotherapy medicine, a platinum medicine and an alkylating agent to preparation of the medicine for preventing or treating the ovarian cancer. Wherein the combined medication can effectively inhibit the growth of ovarian tumor cells and the formation of cell clone, is obviously superior to the single medication, has additive or synergistic effect, has low toxic and side effects on normal cells and high safety, provides a more effective method for treating ovarian cancer, and has important clinical value.

The use of AKR1C3 enzyme-activated DNA alkylating agent prodrug compounds containing aziridine structures, as well as their salts, esters, solvates, and isotopic isomers, in combination with anti-allergy drugs / nonsteroidal analgesics for the treatment of cancer and tumor patients; and the use of AKR1C3 enzyme-activated DNA alkylating agent prodrug compounds containing aziridine structures, as well as their salts, esters, solvates, and isotopic isomers, in combination with anti-allergy drugs / nonsteroidal analgesics in the preparation of drugs for the treatment of cancer and tumors.

The present disclosure relates to macrocyclic ketone compounds that are analogs of DNA-alkylating agent duocarmycin, compositions thereof and methods of making and using the same. The compounds may be used to treat a disease caused or characterized by undesired cell proliferation, such as a tumor.

A method for treating cancer or tumor patients with a negative p53 gene mutation or defect by using a drug containing a DNA alkylating agent prodrug compound alone or in combination with other drugs, and the pharmaceutical use thereof. In particular, the DNA alkylating agent prodrug compound is selected from a hypoxia-activated DNA alkylating agent prodrug compound, an AKR1C3-activated DNA alkylating agent prodrug compound, and a β-D-glucosidase or β-galactosidase-activated DNA alkylating agent prodrug compound.

According to the treatment method, a drug containing a DNA alkylating agent prodrug compound and salts, esters, solvates and isotope isomers of the DNA alkylating agent prodrug compound is combined with a drug for up-regulating p53 protein expression or activating p53 functions to treat cancer and tumor patients. The DNA alkylating agent prodrug compound, a drug of salt, ester, solvate and isotope isomer of the DNA alkylating agent prodrug compound and a drug for up-regulating p53 protein expression or activating a p53 function are combined to be applied to preparation of drugs for treating cancers and tumors. Methods for inhibiting the growth of cells detached from organisms using DNA alkylating agent prodrug compounds and salts, esters, solvates, isotopic isomers thereof in combination with drugs that up-regulate p53 protein expression or activate p53 function. The invention relates to a pharmaceutical composition containing a DNA alkylating agent prodrug compound, a salt, an ester, a solvate and an isotope isomer of the DNA alkylating agent prodrug compound, and a drug for up-regulating p53 protein expression or activating a p53 function. The drug containing the DNA alkylating agent prodrug compound and salts, esters, solvates and isotope isomers of the DNA alkylating agent prodrug compound is combined with a drug containing a p53-MDM2 inhibitor to treat cancer and tumor patients.

The present invention provides an application of bone marrow gene markers in predicting the myeloablative sensitivity to sulfonate alkylating agents, including a method, a computer system, a computer device, and a computer-readable storage medium for predicting the myeloablative sensitivity of a subject to sulfonate alkylating agents, which relates to the field of intelligent medicine. The method includes: acquiring data, acquiring the expression data of gene markers of a sample to be tested; the gene markers include one or more of the following: Lrg1, Lilr4b, H2-Eb1, Ak4; processing the data, inputting the expression data of the gene markers into a constructed prediction model, and the prediction model predicts the myeloablative sensitivity of the subject to sulfonate alkylating agents based on the expression data of the gene markers; and outputting a prediction result.

The disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.

The application belongs to the technical field of drug research and development, and particularly relates to a cyclophosphamide or ethylene imine prodrug compound, and further discloses the use thereof for preparing a liver-targeting alkylating agent. The compound disclosed in the application is based on traditional nitrogen mustard and derivatives thereof and ethylene imine alkylating agents, and is metabolically activated by a prodrug form through liver enzymes, further enhances the selectivity of the related compounds, reduces the influence on normal cells, and is metabolically activated by cytochrome P450 (CYP450) to release active ingredients, and has a good application prospect in treating liver-related cancers.

Provided are an siRNA for inhibiting MGMT gene expression and a conjugate thereof, and a pharmaceutical composition comprising the siRNA or the conjugate. The siRNA and the conjugate thereof can specifically degrade MGMT mRNA by means of base pairing to inhibit MGMT protein production, thereby reducing the dose of an alkylating agent such as TMZ, achieving the effect of reducing the toxic and side effects of the alkylating agent, and having a significant clinical value and good application prospects for tumor treatment.

A method for treating surface of substrate, the method including forming a film including a high molecular weight condensate of a silylation agent on the surface thereof to allow a substrate having a plurality of regions to be modified at modification degrees that are different depending on materials of the regions on a surface of the substrate. The method includes preparing a substrate having a surface including two or more regions having different materials; exposing the surface to a surface treatment agent; and baking the substrate, the method not including rinsing the surface with a liquid between the exposing and the baking, the surface treatment agent including a silylation agent and not a nitrogen-containing heterocyclic compound, the silylation agent including organomonosilane that has 2 to 4 nitrogen atoms bonded to a silicon atom.

The invention relates to a method for treating p53 gene mutation or defect negative cancer and tumor patients by using a single drug containing a DNA alkylating agent prodrug compound or combining with other drugs, and a pharmaceutical application. In particular, the DNA alkylating agent prodrug compound is selected from the group consisting of a hypoxia activated DNA alkylating agent prodrug compound, an AKR1C3 activated DNA alkylating agent prodrug compound, a [beta]-glucosidase ([beta]-D-Glucosidase), or a [beta]-galactosidase ([beta]-galactosidase) activated DNA alkylating agent prodrug compound.

Provided is a method for treating cancer by combining an alkylating agent prodrug and a cell cycle inhibitor. The alkylating agent prodrug may be a prodrug of an AKR1C3 enzyme-activated alkylating agent or a prodrug of a hypoxia-activated alkylating agent. The cell cycle inhibitor may be a CDK inhibitor, a WEE inhibitor, a CHK inhibitor, or an ATR inhibitor.