43 results about "Alkylating antineoplastic agent" patented technology

A method of using a DNA alkylating agent prodrug compound-containing single drug or using the single drug and other drugs in combination for treatment of p53 gene mutation or defect negative cancer and tumor patients, and a pharmaceutical use. 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.

The invention discloses a multifunctional nano-carrier with drug resistance, biotin receptor targeting and hypoxia / low pH dual responsiveness and a preparation method and application thereof, and belongs to the technical field of biomedical polymer materials. The AGT inhibitor conjugate with biotin receptor targeting and low oxygen and low pH dual response provided by the invention comprises a hydrophobic 2-amino-O4-benzyl pteridine group (BD), a low oxygen response group azobenzene (AZO) and a hydrophilic high polymer material modified by biotin (Bio). According to the system, hydrophobic chemotherapeutic drugs can be loaded in a drug carrying system through intermolecular acting force, target biotin receptors on tumor cells and are enriched in tumor tissues by utilizing high permeability and long-term effectiveness of the hydrophobic chemotherapeutic drugs; the tumor microenvironment characterized by low oxygen and low pH can induce azo bond breakage and pH response on the nano-carrier to release BD with AGT activity inhibition and an alkylating agent with anti-tumor activity, so that the drug resistance and anti-tumor activity of the drug are improved, and the targeting property is increased.

A treatment method, wherein a drug containing a DNA alkylating agent prodrug compound and a salt, ester, solvate, and isotopic isomer thereof and a drug upregulating p53 protein expression or activating p53 function are used in combination for treating cancer and tumor patients. Use of the drug containing the DNA alkylating agent prodrug compound and a salt, ester, solvate, and isotopic isomer thereof in combination with the drug upregulating p53 protein expression or activating p53 function in the preparation of a drug for treating cancers and tumors. A method using the DNA alkylating agent prodrug compound and a salt, ester, solvate, and isotopic isomer thereof in combination with the drug upregulating p53 protein expression or activating p53 function in order to inhibit the growth of cells which are separated from organisms. A pharmaceutical composition containing the DNA alkylating agent prodrug compound and a salt, ester, solvate, and isotopic isomer thereof and the drug upregulating p53 protein expression or activating p53 function; the pharmaceutical composition is configured such that the drug containing the DNA alkylating agent prodrug compound and a salt, ester, solvate, and isotopic isomer thereof and a drug containing a p53-MDM2 inhibitor are used in combination for treating cancer and tumor patients.

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 application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an 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.

Use of an AKT inhibitor in the preparation of a drug for preventing or treating ovarian cancer, and use of an AKT inhibitor in combination with other drugs for treating ovarian cancer comprising one or more of a PARP inhibitor, a plant-based chemotherapy drug, an antibiotic chemotherapy drug, a platinum drug and an alkylating agent in the preparation of a drug for preventing or treating ovarian cancer. The combined administration can effectively inhibit the growth of ovarian tumor cells and cell colony formation, and is significantly superior to the administration of a single drug. In addition, the combined administration has an additive or synergistic effect, has few toxic side effects on normal cells and has a high safety, provides a more effective method for treating ovarian cancer, and has an important clinical value.

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.

The invention provides an application of a bone marrow gene marker in predicting the marrow cleaning sensitivity of a sulfonic acid alkylating agent, comprises a method for predicting the marrow cleaning sensitivity of a subject to the sulfonic acid alkylating agent, a computer system, computer equipment and a computer readable storage medium, and relates to the field of intelligent medical treatment. The method comprises the following steps: acquiring data: acquiring expression data of a gene marker of a sample to be detected; the gene marker is prepared from one or more of the following components: Lrg1, Lilr4b, H2-Eb1, Ak4, Glg2, Glg2, Glg2, Glg2, Glg2, Glg2, processing the data, inputting the expression data of the gene marker into a constructed prediction model, and predicting the sensitivity of the subject to the marrow removal of the sulfonic acid alkylating agent by the prediction model based on the expression data of the gene marker; and outputting a prediction result.

The invention provides a method and application for treating cancer by combining a CD20 / CD47 double-blocking bifunctional fusion protein with a bifunctional alkylating agent, in particular a method and application for treating cancer (particularly non-Hodgkin's lymphoma) by combining the CD20 / CD47 double-blocking bifunctional fusion protein with bendamustine or a salt thereof.

To provide a method for rapidly synthesizing a variety of C-terminal-free N-substituted peptides in a high yield while suppressing epimerization.SOLUTION: The present invention provides a method for producing an N-substituted peptide represented by the following formula (6), comprising a step of reacting a first amino acid represented by the following formula (1), a second amino acid represented by the following formula (2), a silylating agent, a condensing agent, a tertiary amine, and an imidazole derivative.SELECTED DRAWING: None

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.

To provide therapeutic methods for treating kidney diseases.SOLUTION: There are provided therapeutic methods for treating kidney diseases, using compounds of Formula (A) in combination with a second therapeutic agent. (In the formula: each R is independently selected from a group comprising H, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, halogen, -OH, CN, cycloalkyl, -O-alkyl, -O-cycloalkyl, -O-aryl, -aryl-O-aryl, -CF3, -C(H)F2, alkylene-CF3, alkylene-C(H)F2, -SO2-alkyl, -O-alkylene-O-alkyl, -heterocyclyl-L-R4, and heteroaryl-L-R4; and only one R is -heterocyclyl-L-R4 or -heteroaryl-L-R4). The second therapeutic agent is selected from an immunomodulator, a calcineurin inhibitor, a renin angiotensin aldosterone system inhibitor, an antiproliferative agent, an alkylating agent, and the like.SELECTED DRAWING: None

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.

An object of the present invention is to provide a new combination of antitumor agents, which can significantly reduce tumors through synergistic antitumor effects while minimizing the increase of side effects. The present invention provides an antitumor composition, which comprises the following compound (B) or a salt thereof used in combination with the following antitumor agent (A): (A) at least one antitumor agent selected from alkylating agents, CD20 recognition molecules, DNA methylation inhibitors, pyrimidine antimetabolites, purine antimetabolites, antifolate agents, Bcl-2 inhibitors and tyrosine kinase inhibitors; (B) a compound represented by the following formula (1) or a salt thereof: wherein R 1 represents a halogen atom, an aryl group, an aryloxy group or a lower alkyl group optionally substituted by one or more halogen atoms; R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; m represents an integer from 1 to 3, provided that when m represents 2 or 3, R 1 Same or different.

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.

The present application relates to the use of a VRAC modulator of formula I or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of cancer in combination with an anti-cancer therapeutic agent, wherein the anti-cancer therapeutic agent is selected from the group consisting of topoisomerase inhibitors, antihormones, alkylating agents, antimetabolites, anti-tumor antibiotics, corticosteroids, targeted anti-cancer therapies, differentiation agents, and immunotherapies. # imgabs0 #

The invention relates to an anti-tumor composition. The antitumor composition comprises the following compound (B) or a salt thereof used in combination with the following antitumor agent (A): (A) at least one antitumor agent selected from the group consisting of an alkylating agent, a CD20 recognition molecule, a DNA methylation inhibitor, a pyrimidine-based antimetabolite, a purine-based antimetabolite, an antifolic acid-based agent, a Bcl-2 inhibitor, and a tyrosine kinase inhibitor; (B) a compound represented by the following formula (1), or a salt thereof, wherein R1 represents a halogen atom, an aryl group, an aryloxy group, or a lower alkyl group optionally substituted by one or more halogen atoms; r2 represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group; and m represents an integer of 1 to 3, with the proviso that when m represents 2 or 3, R1 may be the same or different. The anti-tumor composition can significantly inhibit the growth of tumor cells. # imgabs0 #

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 of treating cancer using an alkylating agent prodrug in combination with a cell cycle inhibitor, the alkylating agent prodrug may be an AKR1C3 enzyme activated alkylating agent prodrug or a hypoxic activated alkylating agent prodrug, and the cell cycle inhibitor may be a CDK inhibitor, a WEE inhibitor, a CHK inhibitor or an ATR inhibitor.