191 results about "Topoisomerase inhibitor" patented technology

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of LAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inbhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

The present Invention relates to a method of treating abnormal cell growth in a subject, comprising administering to said subject having abnormal cell growth: (a) a compound selected from the group consisting of a camptothecin, a camptothecin derivative, or a pharmaceutically acceptable salt, solvate or prodrug of said compounds; (b) a pyrimidine derivative or a pharmaceutically acceptable salt, solvate or prodrug of said pyrimidine derivative; and (c) an anti-tumor agent selected from the group consisting of antiproliferative agents, kinase inhibitors, angiogenesis inhibitors, growth factor inhibitors, cox-I inhibitors, cox-II inhibitors, mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, radiation, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxics, anti-hormones, anti-androgens and combinations thereof.

Provided are methods relating to compositions that include a CDP-topoisomerase inhibitor, e.g., a CDP-camptothecin or camptothecin derivative conjugate, e.g., CRLX101.

The invention relates to the technical field of medicines. The content of DNA topoisomerase I (TopoI) in tumor cells is substantially higher the content of the TopoI in normal tissues, and an inhibitor of the TopoI is listed as one of six types of antitumor drugs which are primarily researched by an American NCI (National Cancer Institute). The invention aims to obtain evodiamine derivatives withstrong antitumor activities by modifying the structure of evodiamine. The evodiamine structure of the evodiamine compounds is represented by general formula (I) in the specification. The invention also provides an application of the evodiamine compounds and medicinal salts thereof in preparing topoisomerase inhibitors and antitumor drugs.

A pharmaceutical combination comprising a topoisomerase II inhibitor, and an Hsp90 inhibitor according to the following formulae 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.

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 present invention relates to pharmaceutical compositions and methods for the mucosal and oral administration of monoterpenes and derivatives thereof. The compositions of this invention further comprise one or more surfactants and cosolvents and are in the form of self-emulsifying compositions. The compositions of the invention may further comprise water-insoluble therapeutic agents, vaccines and diagnostics. Such agents include but are not limited to taxanes, steroids, topoisomerase inhibitors such as etoposide and other water-insoluble or lipophilic drugs.

The invention provides a butyrylcholinesterase variant having the amino acid sequence selected from SEQ ID NOS: 4, 6, 8, 10, 12, 14, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, and 196, or functional fragment thereof. In addition, the invention provides a method of converting a camptothecin derivative to a topoisomerase inhibitor by contacting the camptothecin derivative with a butyrylcholinesterase variant selected from SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, and 196, or functional fragment thereof, under conditions that allow conversion of a camptothecin derivative to a topoisomerase inhibitor. Further, the invention provides a method of treating cancer by administering to an individual an effective amount of a butyrylcholinesterase variant selected from SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, and 196, or functional fragment thereof, exhibiting increased capability to convert a camptothecin derivative to a topoisomerase inhibitor compared to butyrylcholinesterase.

Disclosed inter alia is the use of quinazolinone derivatives, which are modulators of a mitotic kinesin such as KSP, in the treatment of cellular proliferative diseases. The quinazolinone derivatives are administered with another chemotherapeutic agent selected from alkylating agents, antimetabolites, platinating agents, topoisomerase inhibitors, tubulin agents and signalling inhibitors (e.g., kinase inhibitors). Pharmaceutical compositions comprising one or both types of active agents are also disclosed.

The administration of cytotoxic agents followed by the administration of heat shock protein 90 inhibitors, such as ansamycins, has a synergistic effect on the growth inhibition of cells. This synergy occurs at doses of each cytotoxic agent that normally only causes minimal growth inhibition of cells. Such combination therapy thus allows one to use lower doses of cytotoxic agents to avoid or reduce their respective toxicity to patients without compromising their growth inhibitory effects. Thus, these combinations can be used for the treatment of an animal, preferably a mammal, that has a cell proliferative disorder, whether the cells have wild-type Rb or are Rb deficient or Rb negative. One such method, directed to treating cell proliferative disorders includes the step of administering a therapeutic effective amount of a cytotoxic agent followed by administering a therapeutic effective amount of a heat shock protein 90 inhibitor. The cytotoxic agent may be a microtubule-affecting agent, topoisomerase II inhibitor, a platinum complex, paclitaxel, or a paclitaxel derivative. The HSP90 inhibitor may be an ansamycin, radicicol or a synthetic compound that binds to the ATP-binding site of HSP90.

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 application is directed to compounds, intermediates and methods for preparing compounds of formula (I)

or a pharmaceutically acceptable salts thereof, wherein R is H or F, and each of R₃, R₄, and R₅ are as defined herein. The compounds of formula (I) and pharmaceutical compositions comprising said compounds and salts inhibit bacterial gyrase and/or Topo IV and are useful in treating bacterial infections.

The present invention provides methods and compositions for inducing expression of Ube3a in a cell by contacting the cell with a topoisomerase inhibitor. Particular embodiments include a method of treating a genomic imprinting disorder, such as Angelman syndrome, in a subject by administering to the subject an effective amount of a topoisomerase inhibitor.

The invention discloses a beta-carboline derivative containing hydroximic acid as well as a preparation method and a medical application thereof. The product has the structure as shown in the general formula I. The compound can be combined with other antitumor drugs such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors and DNA intercalating agents and additionally can be combined with radiotherapy. The invention also discloses a pharmaceutical composition containing the compound with the general formula I as well as medical application thereof, particularly application of preparation of antitumor medicines, Alzheimer disease medicines and Parkinson disease medicines. The other antitumor medicines or radiotherapy can be administrated with the compound at the same time or in different times. The combination therapy can generate the synergistic effect, so that the treatment effect is improved.

The present invention relates to a compound of formula (I)

or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti-bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

The invention discloses an acridine derivative represented by the formula I and a preparation method and application thereof. The formula I represents a compound or a medically accepted salt, ester and solvent composition thereof; Z is NHCH2, NHCH2CH2, NHCH2CH2CH2 or OCH2; the compound represented by the formula I has a deoxyribonucleic acid (DNA) connection function and inhibition activity to topoisomerase; the compound or the medically accepted salt, ester and solvent composition thereof can be effectively used for preparing a DNA connector, a topoisomerase inhibitor and an eucaryon biological tumor cell multiplication inhibitor and tumor preventing and/or treating medicines.

This invention relates a method of treating hyperproliferative diseases. More particularly, the present invention relates to a method of treating hyperproliferative diseases, such as cancer, comprising the step of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a therapeutically effective amount of a taxane derivative, a platinium coordination complex selected from the group consisting of carboplatin, tetraplatin, and topotecan, a nucleoside analog selected from the group consisting of gemcitabine hydrochloride and 5-FU, an anthracycline, a topoisomerase selected from the group consisting of etoposide, teniposide, amsacrine, topotecan, and Camptosar®, an aromatase inhibitor; and (ii) a therapeutically effective amount of an isothiazole derivative. The combinations of the present invention may optionally include an anti-hypertensive agent. This invention also relates to pharmaceutical compositions useful in the treatment of hyperproliferative diseases in mammals, containing such combinations. The present invention also relates to kits having a first compartment with a compound of formula 1 and a second compartment containing a taxane derivative, a platinum coordination complex, a nucleoside analog, an anthracycline, a topoisomerase inhibitor, or an aromatase inhibitor and a third compartment containing an anti-hypertensive agent.

The invention provides a butyrylchinesterase variant, a method of converting a camptothecin derivative to a topoisomerase inhibitor by contacting the camptothecin derivative with a butyrylcholinesterase variant and a method of treating cancer by administering to an individual an effective amount a butyrylcholinesterase variant exhibiting increased capability to convert a camptothecin derivative to a topoisomerase inhibitor compared to butyrylcholinesterase.

The present invention relates to phosphate esters of compounds that inhibit bacterial gyrase and/or Topoisomerase IV and pharmaceutical compositions thereof. These phosphate esters are useful for treating bacterial infections.

Disclosed and claimed are cocoa extracts such as polyphenols or procyanidins, methods for preparing such extracts, as well as uses for them, especially as antineoplastic agents and antioxidants. Disclosed and claimed are antineoplastic compositions containing cocoa polyphenols or procyanidins-and methods for treating patients employing the compositions. Additionally disclosed and claimed is a kit for treating a patient in need of treatment with an antineoplastic agent containing cocoa polyphenols or procyanidins as well as a lyophilized antineoplastic composition containing cocoa polyphenols or procyanidins. Further, disclosed and claimed is the use of the invention in antioxidant, preservative and topiosomerase-inhibiting compositions and methods.

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inbhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

The invention relates to novel benzanthracene cyclic compounds and a preparation method and use thereof. The benzanthracene cyclic compounds have the structure shown in a general formula I or II. The compounds can be used as topoisomerase inhibitors for preparing anti-tumor, cell growth-resistant, antibacterial and antimalarial medicaments. The invention also relates to a method for preparing the compounds. In the formula I, C1' and C3' have an S structure simultaneously, and in the formula II, C1' and C3' have an R structure simultaneously.

The invention provides a method of treating neoplastic disease in a subject, said method comprising the simultaneous, sequential or separate, administration to said subject of an effective amount of (i) an inhibitor of a first EGF, e.g. HB-EGF and (ii) an inhibitor of a second EGF, e.g. AREG. Also described are novel synergistic combinations of EGF inhibitors with topoisomerase inhibitors which attenuate tumour cell growth. Further described are novel anti AREG antibodies.