71 results about "Topoisomerase-I Inhibitor" patented technology

Methods and compositions for modulating the FGF effect on the sensitivity of malignant and normal cells to anticancer agents are provided. In particular, methods and compositions for inhibiting FGF-induced resistance to a broad spectrum of anticancer agents in solid and soft-tissue tumors, metastatic lesions, leukemia and lymphoma are provided. Preferably, the compositions include at least one FGF inhibitor in combination with a cytotoxic agents, e.g., antimicrotubule agents, topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites, mitotic inhibitors, alkylating agents, intercalating agents, agents capable of interfering with a signal transduction pathway (e.g., g., a protein kinase C inhibitor, e.g., an anti-hormone, e.g., an antibody against growth factor receptors), an agent that promotes apoptosis and / or necrosis, and interferon, an interleukin, a tumor necrosis factor, and radiation. In other embodiments, methods and composition for protecting a cell in a subject, from one or more of killing, inhibition of growth or division or other damage caused, e.g., by a cytotoxic agent, are provided. Preferably, the method includes: administering, to the subject, an effective amount of at least one FGF agonist, thereby treating the cell, e.g., protecting or reducing the damage to the dividing cell from said cytotoxic agent.

The present invention relates to a pharmaceutical composition, a kit, a method of treating cancer and / or a method of inhibiting angiogenesis comprising a sulfonamide compound in combination with a platinum complex, a DNA-topoisomerase I inhibitor, an antimetabolite, a microtubule inhibitor or an antibiotic.

The invention discloses a method for predicating a homologous recombination deficiency (HRD) mechanism and a method for predicating response of patients to cancer therapy and relates to the field of biological information predication. The method comprises the step of judging whether a tumor sample has homologous recombination deficiency or not according to one or more comprehensive values in a large-segment INDEL (Insertion / Deletion) fraction, a copy number variation fraction and a tumor mutation load fraction, wherein the comprehensive values can also comprise a loss of heterozygosity variation fraction. By adopting the method disclosed by the invention, predication of a chromosome large-segment structure, a chromosome gene type number, a chromosome gene copy number, a chromosome variation interval and abnormal loss of heterozygosity and chromosome telomeric imbalance is realized, so that an evaluation range is more complete and HRD can be accurately predicated; the comprehensive values also can be used for determining whether the patients have response to a therapeutic regimen containing one or more of a PARP (Poly Adenosine Diphosphate Ribose Polymerase) inhibitor, an DNA (Deoxyribonucleic Acid) injury inhibitor, a topoisomerase II / II+inhibitor, a topoisomerase I inhibitor and radiotherapy; the method is simple and has wide general applicability.

The invention relates to the technical field of medicines and in particular relates to oxa- or thio-evodiamine anti-tumor derivatives as well as a preparation method of the derivatives and application of the derivatives in preparation of topoisomerase inhibitors and anti-tumor drugs. The oxa- or thio-evodiamine anti-tumor derivatives are newly discovered topoisomerase I inhibitors with brand-new structures and have remarkable anti-tumor activity, and the structure of a compound is as shown in a general formula I.

The invention relates to the technical field of medicine, in particular to a new benzoxanthone type compound and an application thereof in pharmacy. Benzoxanthone type derivatives are one type of topoisomerase I inhibitors in new structure, which are found in recent years, and have obvious cell proliferation activity. The invention provides the new benzoxanthone type compound and pharmaceutical salts thereof, and the structure of the compound is as shown in the general formula (I). The invention further provides the application of the benzoxanthone type compound and the pharmaceutical salts thereof in the preparation of the topoisomerase inhibitors, anti-tumor medicaments, antifungal medicaments, antiviral medicaments, anti-hypertensive medicaments or anti-thrombotic medicaments.

The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of an alkylating or alkylating-like agent, an antimetabolite agent, a topoisomerase I inhibitor, a topoisomerase 11 inhibitor, an inhibitor of a growth factor or of a growth factor receptor, an antimitotic agent, a proteasome inhibitor, an inhibitor of an anti-apoptotic protein and an antibody directed against a cell surface protein, wherein the active ingredients are present in each case in lice form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.

A pharmaceutical combination comprising a topoisomerase I inhibitor, and an Hsp90 inhibitor according to the following formulae (I) (Ia) a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables in the structural formulae are defined herein. Also provided is a method for treating a proliferative disorder in a subject in need thereof, using the pharmaceutical combination described herein.

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4 / 6 (CDK4 / 6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

The present invention provides combinations of a Cox-2 inhibitor and a DNA topoisomerase inhibitor and methods of use thereof for preventing and / or treating neoplasia or or a neoplasia-related disorder in a subject.

The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer.

The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer.

The invention relates to formyl phloroglucinol hetero terpenoids separated out from fruit of eucalyptus globulus, pharmaceutical compositions taking the formyl phloroglucinol hetero terpenoids as active components, preparation methods of the formyl phloroglucinol hetero terpenoids and the pharmaceutical compositions as well as applications of the formyl phloroglucinol hetero terpenoids and the pharmaceutical compositions in preparation of medicines for treating tumors and in preparation of functional health care products. The methods provided by the invention are easy in obtaining of raw materials, simple and easy to operate; biological experiments prove that the obtained compounds have better activity of inhibiting the growth of tumor cells; furthermore, the compounds 1, 2, 3 and 5 have aDNA inhibiting topoisomerase I (TOP1) activity similar to camptothecin, and the compounds 1 and 4 have a better activity of promoting cancer cell apoptosis.

The invention discloses a method for fast screening a topoisomerase I inhibitor from a natural product, and relates to the analysis field of natural products. The method comprises the following steps of: (1) preparation of an enzyme binding reaction buffer solution; (2) preparation of a to be detected sample; (3) preparation of a standard solution; (4) binding reaction of the to-be-detected sample and normal and inactive topoisomerase I; (5) chromatography-mass spectrometry detection analysis of reaction sample; and (6) enrichment ratio of the topoisomerase I to the inhibitor. The ultrafiltration membrane technology and the chromatography-mass spectrometry united technology united method are applied to the screening of the topoisomerase I inhibitor, the sample analysis speed is fast and the specificity is strong so as to conveniently recognize a medicine ligand combined with a biological target molecule; meanwhile, the sample analysis dosage is less, and the spectrogram information quantity is large so as to realize the fast screening of the lead compound, the method has great advantage on the aspect of researching mutual effect of medicine small molecule ligand and biological macromolecule receptor; the method is suitable for analyzing in-vitro enrichment ratio of the natural product extract or monomer compound to the topoisomerase I inhibitor.

The present invention relates to pharmaceutical compositions comprising a topoisomerase I inhibitor including, but not limited to, a camptothecin derivative.

The present invention relates to nanoparticulate compositions in which the active agent is a topoisomerase I inhibitor and pharmaceutical compositions comprising the nanoparticulate compositions that are useful for the treatment and prevention of proliferative diseases including cancer.

The present invention relates to pharmaceutical compositions comprising a topoisomerase I inhibitor including, but not limited to, a camptothecin derivative.

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4 / 6 (CDK4 / 6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

The present invention generally relates to the fields of cancer therapy and cancer prevention. More particularly, the present invention generally relates to a diagnostic marker for predicting the efficacy of topoisomerase I (topo I) inhibitors in the treatment of cancers. More specifically, the present invention relates to methods, machines, computer systems, computable readable media and kits which can be used to identify and determine the effectiveness of topoisomerase I (topo I) inhibitors in the treatment of cancers, and in some embodiments, the level of sensitivity or resistance of a tumor cell to a topoisomerase I inhibitor, such as camptothecin (CPT), or CTP analogues such as topotecan and irinotecan and derivatives thereof. More specifically, the present invention related to methods, machines, computer systems, computable readable media and kits which can be used to determine the presence of phosphorylation of topoisomerase I polypeptide, in some embodiments phosphorylation at residue serine 10 (S10) of a topoisomerase I polypeptide, wherein the presence of phosphorylation, in particular the phosphorylation at serine 10 of a topoI polypeptide indicates a cancer is likely to be unresponsive to a topo I inhibitor, whereas the absence of phosphorylation, in particular, the absence of phosphorylation at residue serine 10 (S10) identifies a cancer is likely to be responsive to a topo I inhibitor. Other aspect of the present invention relate to phospho-serine 10 topoisomerase I antibodies and other protein binding moieties, and uses thereof.

The invention described herein pertains to substituted indenoisoquinoline compounds as described herein, wherein RA, RD, W, X and Y are defined herein, pharmaceutical compositions and formulations comprising the indenoisoquinoline compounds, their synthesis, and methods for their use in the treatment and / or prevention of cancer.

A method to treat cancer is described which involves alternating treatments with a topoisomerase-I inhibitor and a topoisomerase-II inhibitor. Other aspects of the invention are further described.

This invention relates to crystalline structures of the topoisomerase I and their use in designing new anti-cancer agents anti-viral agents and anti-microbial agents.

The invention described herein pertains to substituted indenoisoquinoline compounds as described herein, wherein RA, RD, W, X and Y are defined herein, pharmaceutical compositions and formulations comprising the indenoisoquinoline compounds, their synthesis, and methods for their use in the treatment and / or prevention of cancer.

The present invention relates to peptide conjugates of cytotoxins such as topoisomerase I inhibitors which are useful for the treatment of diseases such as cancer.

The invention described herein pertains to substituted azaindenoisoquinoline compounds, in particular 7-, 8-, 9-, and 10-azaindenoisoquinoline compounds, which are inhibitors of topoisomerase I, processes and intermediates for their syntheses, pharmaceutical compositions of the compounds, and methods of using them in the treatment of cancer.

The present invention discloses a sensor chip for screening a topoisomerase inhibitor and a screening method thereof. The sensor chip comprises topoisomerase I and a biochip. The topoisomerase I is immobilized on the biochip, and the topoisomerase I has DNA catalytic activity. This provides a rapid screening method for topoisomerase I inhibitors.

Disclosed herein are methods and compositions for enhancing the sensitivity of cells to the effects of topoisomerase I inhibitors. Also disclosed are methods and compositions for inducing apoptosis and / or growth arrest which may be used for tumor suppression.