34 results about "Ansamycin" patented technology

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.

Ansamycins and methods of preparing and using the same are described. At least some of these ansamycins exhibit one or more of improved aqueous formulation ability, chemical stability, and bioavailability. Some of the derivatives described are dimers. These and others described can include one or more solubilizing groups that have expected merit in rendering the overall compounds useful as drugs and prodrugs.

Ansamycin formulations and methods of producing and using the same are described and claimed. The formulations are emulsions that can be used directly in a patient, or be lyophilized and / or frozen, to be later used, e.g., upon re- or further hydration or processing.

The invention relates to benzoquinone ansamycin analogs useful for the treatment of cancer and other diseases or conditions characterized by undesired cellular proliferation or hyperproliferation. Therapies involving the administration of such benzoquinone ansamycin analogs, optionally in combination with an inhibitor of an HSP90 client protein, are useful to treat cancer and non-cancerous disease conditions.

The present invention provides cancer treatment preparations of excellent targetability. The sugar chain-modified liposomes of the present invention, which contain an aromatase inhibitor, anti-androgenic agent, lyase inhibitor, GnRH agonist, GnRH antagonist, anti-angiogenic agent, tyrosine kinase inhibitor, serine-threonine kinase inhibitor, antibody having an anticancer activity, ansamitocin, capecitabine, celmoleukin, docetaxel hydrate, gemcitabine hydrochloride, oxaliplatin, prednisolone, tegafur-uracil mixtures, zinostatin stimalamer or arsenic trioxide may be used as cancer treatment preparations having an excellent targetability.

The present invention relates to geldanamycin high yield engineered bacteria strain construction, It is specificly described as follows: two groups of AHBA synthase gene cluster AHBA-shn gene discovered in water-absorbing streptomyces are destroyed by gene blocking technology due to likely participation in naphthoquinone type ansamycin compound biosynthesis. The present invention increases benzenquinone type GDM precursor (B-AHBA) supply and metabolic flow to promote GDM ferment yield by blocking or reduceing content of naphthoquinone type ansamycin compound precursor (N-AHBA). It proves that block mutant strain promote near 186% in yield to original strain.

The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

The present invention provides inter alia derivatives of a benzenoid ansamycin which contain a 1,4-dihydroxyphenyl moiety bearing at position 6 an amino carboxy substituent, in which position 2 and the carboxy substituent at position 6 are connected by an aliphatic chain of varying length characterised in that one or both of the 1-hydroxy and the 4-hydroxy position(s) of the phenyl ring are independently derivatised by an aminoalkyleneaminocarbonyl group, which alkylene group, which may optionally be substituted by alkyl groups, has a chain length of 2 or 3 carbons and which derivatising group(s) increase the water solubility and / or the bioavailability of the parent molecule but which are capable of being removed in-vivo. Such compounds are described for the treatment of cancer or B-cell malignancies.

2-Desmethyl ansamycins having a structure according to formula I, where R1, R2, R3, R4, R5 and R6 are as defined herein, and other 2-desmethyl ansamycins are useful as antiproliferative agents

Geldanamycin derivatives that block the uPA-plasmin network and inhibit growth and invasion by glioblastoma cells and other tumors at femtomolar concentrations are potentially highly active anti-cancer drugs. GA and various 17-amino-17-demethoxygelddanamycin derivatives are disclosed that block HGF / SF-mediated Met tyrosine kinase receptor-dependent uPA activation at fM levels. Other ansamycins (macbecins I and II), GA derivatives, and radicicol required concentrations several logs higher (>=nM) to achieve such inhibition. The inhibitory activity of tested compounds was discordant with the known ability of drugs of this class to bind to hsp90, indicating the existence of a novel target(s) for HGF / SF -mediated events in tumor development. Methods of using such compounds to inhibit cancer cell activities and to treat tumors are disclosed. Such treatment with low doses of these highly active compounds provide an option for treating various Met-expressing tumors, in particular invasive brain cancers, either alone or in combination with conventional surgery, chemotherapy, or radiotherapy.

The invention relates to a medicinal composition having tumor-resistant synergy. The composition consists of a lidamycin olefin diyne type antibiotic, a geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof. Research shows that the geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof, which serve as a chemical therapy sensitivity enhancer, can inhibit the restoration of the DNA damaged by DNA damage medicaments, and achieve a synergic effect for treating tumor when used in combination with the chemical therapy medicament of the lidamycin olefin diyne type antibiotic.

Provided herein, inter alia, are solid forms of geldanamycin analogs, pharmaceutical compositions comprising a geldanamycin analog and a crystallization inhibitor, methods of making and using such compositions. Additionally, provided are methods for the treatment of cancer, a neoplastic disease state and / or a hyperproliferative disorder, and methods of inhibiting Heat Shock Protein 90 (“Hsp90”).

The invention relates to a medicinal composition having tumor-resistant synergy. The composition consists of a lidamycin olefin diyne type antibiotic, a geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof. Research shows that the geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof, which serve as a chemical therapy sensitivity enhancer, can inhibit the restoration of the DNA damaged by DNA damage medicaments, and achieve a synergic effect for treating tumor when used in combination with the chemical therapy medicament of the lidamycin olefin diyne type antibiotic.

Ansamycin analogs, including maytansinoid analogs, and their use in treating cell proliferative diseases and conditions, and in particular, for use as antitumor agents.

The present invention relates to ansamycin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases or a prophylactic pretreatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine.

The present invention relates to geldanamycin high yield engineered bacteria strain construction, It is specificly described as follows: two groups of AHBA synthase gene cluster AHBA-shn gene discovered in water-absorbing streptomyces are destroyed by gene blocking technology due to likely participation in naphthoquinone type ansamycin compound biosynthesis. The present invention increases benzenquinone type GDM precursor (B-AHBA) supply and metabolic flow to promote GDM ferment yield by blocking or reduceing content of naphthoquinone type ansamycin compound precursor (N-AHBA). It proves that block mutant strain promote near 186% in yield to original strain.