44 results about "Topoisomerase-II Inhibitor" patented technology

The present invention provides methods for diagnosing and treating cancer, and in particular methods for determining the susceptibility of subjects suspected of having breast cancer (or known to have breast cancer) to treatment with topoisomerase II inhibitors. The present invention also provides in situ hybridization probes for specifically detecting topoIIα gene sequences.

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 an antitumor agent containing a histone deacetylase inhibitor and a topoisomerase II inhibitor in combination. This combination has been found to exhibit a synergistic anticancer or antitumor effect compared to administration of either the histone deacetylase alone or the topoisomerase II inhibitor alone. Thus, this combination provides a tumor or cancer treatment with fewer side effects since a lower dosage of both ingedients may be administered.

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 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.

Maleimide and succinimide derivatives were found to be effective topoisomerase II catalytic inhibitors. Due to this property, the maleimide and succinimide derivatives were investigated for their use as cytostatic agents and thus in the treatment of cancer. The compounds of the invention can be used in combination treatments with other cytostatic agents, such as topoisomerase II poisons. The maleimide and succinimide derivatives, due to their effective topoisomerase II catalytic inhibitory activity, are also useful as extravasation agents, such as upon administration of a topoisomerase II poison.

An aminocoumarin conjugated to a fluorescent label through a secondary amine, is operative as a fluorescent polarization probe of the DNA gyrase B or topoisomerase IV E subunit. The probe is used for detecting topoisomerase inhibitor binding by fluorescence polarization, particularly in a high-through put topoisomerase inhibitor assay.

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.

Disclosed are methods and compositions useful in identifying an E3 ubiquitin ligase inhibitor and modulating cell growth, comprising contacting a cell with an effective amount of an inhibitor of an E3 ubiquitin ligase, and contacting the cell with an effective amount of a topoisomerase inhibitor, wherein the treatment with the E3 ubiquitin ligase inhibitor and topoisomerase inhibitor modulates cell growth in comparison to a cell treated with the topoisomerase inhibitor alone. The present invention further provides methods for identifying and making an E3 ubiquitin ligase inhibitor.

The instant invention provides a continuous spectroscopic assay for DNA topoisomerase activity. The invention further provides topoisomerase inhibitors and pharmaceutical compositions for the treatment of topoisomerase associated diseases and disorders.

The present invention provides compositions and methods to treat, prevent or inhibit a neoplasia or a neoplasia-related disorder in a mammal using a combination of a COX-2 inhibitor and a topoisomerase II inhibitor.

The invention provides combination therapies and methods for the treatment of cancers associates with p53 mutations. The method comprises the separate, sequential or simultaneous administration of a therapeutically effective amount of a) a specific binding member, for example CH-11, which binds to a cell death receptor, for example Fas, or a nucleic acid encoding said binding member and b) a chemotherapeutic agent, wherein the chemotherapeutic agent is a topoisomerase inhibitor, for example CPT-1 or a thymidylate synthase inhibitor, for example TDX. Synergistic cytotoxic effects have been demonstrated using such combinations.

A combination therapy for treating patients suffering from proliferative diseases or diseases associated with persistent angiogenesis is disclosed. The patient is treated with a camptothecin derivative and one or more chemotherapeutic agents selected from a microtubule active agent; an alkylating agent; an anti-neoplastic anti-metabolite; a platin compound; a topoisomerase II inhibitor; a VEGF inhibitor; a tyrosine kinase inhibitor; an EGFR kinase inhibitor; an mTOR kinase inhibitor; an insulin-like growth factor I inhibitor; a Raf kinase inhibitor; a monoclonal antibody; a proteasome inhibitor; a HDAC inhibitor; and ionizing radiation.

Pharmaceutical compositions comprising two or more therapeutically active agents, such as two or more anticancer agents, conjugated to one or more biocompatible polymers, wherein the molar ratio of the agents and/or schedules of delivery provide a synergistic therapeutic effect, are described. Methods of making and using the pharmaceutical compositions are further described. In one embodiment, the pharmaceutical compositions contain topoisomerase I and topoisomerase II inhibitors conjugated to the same or different biocompatible polymers. The two or more anticancer agents are covalently coupled to the polymer(s), and thereby can be delivered to a tumor at a molar ratio which provides a synergistic effect. Optionally, the agents are coupled indirectly to the polymer(s) via a linker.

The present Invention relates to a method of treating a warm-blooded animal having acute myeloid leukemia (AML) which is resistant to conventional chemotherapy, comprising administering to said animal a therapeutically effective amount of a compound of formula (I), wherein the radicals and symbols have the meanings as defined in the specification, together or in combination with a conventional compound or compound mixture useful in AML treatment, in particular a topoisomerase II inhibitor, an antimetabolite, or an antitumor antibiotic, for simultaneous, separate or sequential use; and to a pharmaceutical composition and a commercial package comprising said combination.

A method of treating cancer in a subject comprising the step of administering to the subject in need thereof an effective amount of a combination of a compound that binds a nuclear export signal (NES inhibitor) on topoisomerase IIα and a topoisomerase inhibitor. Twenty small molecule inhibitors (SMI) that bind to the two nuclear export sequences (NES) topo IIα have been identified from the NCI database using computer-generated molecular modeling. These SMI will improve the effectiveness of topo II directed therapeutics, particularly in the treatment of diseases such as multiple myeloma (MM). In vitro apoptosis assays indicate that these drugs may be effective as single agents or in combination with currently used cancer drugs that target topo II.

A temperature control sustained release injection comprising topoisomerase inhibitor is composed of the topoisomerase inhibitor with an effective anti-cancer amount, an amphiphilic block copolymer, menstruum, and medicine release regulator with a fixed amount; wherein, the amphiphilic block copolymer consists of polyethylene glycol and polyester and an aqueous liquid of the amphiphilic block copolymer under a room temperature can change into a semi-solid or solid gel which can be absorbed by biodegradation and insoluble in water in a body of a hot blood animal; thereby being able to slowly release the Polyphosphate 3-Kinase inhibitor comprised in partial knub for a plurality of weeks to a plurality of months; an anti-cancer sustained release injection, being injected in the knub or in the surroundings of the knub or being arranged in a knub cavity after operation, can remarkably reduce the general reaction of the medicine, selectively enhance the curing effects of non operative treatments like chemotherapy and radiotherapy, and is used for curing the knub of different stages. The topoisomerase inhibitor is selected from self-hydroxy camptothecin, lartotecan, topotecan, irinotecan, etoposide, teniposid, podophyllotoxin, amrubicin, doxorubicin, esorubicin, pirarubicin and valrubicin.

The invention provides a benzimidazole derivative which is provided with a structure as shown in a formula (I). R1 and R2 are independently selected from one of hydrogen, halogen, alkyl, alkoxy, halogenated alkyl, nitryl and a nitrile group, R3 is carboxyl, alkyl, phenyl or a cyano group, the value range of m is 0-3, the value range of n is 0-3, X is CH or nitrogen, and Y is CH2 or carbonyl. The benzimidazole derivative has a strong inhibiting effect on activity of topoisomerase II, so that the benzimidazole derivative can serve as a topoisomerase II inhibitor. Research finds that the compoundis the catalytic inhibitor of Topo II, so that the compound can be used for preparing an anti-tumor drug taking the topoisomerase II as a target spot. Besides, the benzimidazole derivative has good anti-proliferative activity for a plurality of tumor cells, so that the benzimidazole derivative can be used for preparing the anti-tumor drug.

The invention relates to an application of a saponin compound echinoside A extracted from sea cucumber in preparing tumor topoismerase II inhibitors, belonging to the technical field of pharmaceuticals. The compound echinoside A has a molecular formula of C54H87O26SNa, and the chemical structure and the spatial configuration of the compound are determined through analysis of multiple modern spectra including advanced two-dimensional nuclear magnetic resonance spectra. In vitro tests indicate that the compound has distinct inhibitory effect on tumor topoismerase II (Topo II), and is an effective Topo II inhibitor. The invention provides a lead compound for developing Topo II inhibitors, and is important for developing and unitizing Chinese ocean medicinal biological resources.

Topoisomerase inhibitors are useful for the treatment of inflammatory disorders including arthritis, restenosis, surgical adhesions and other diseases. Controlled release polymeric formulations to topoisomerase inhibitors are particularly suitable for this use.