61 results about "Epothilone" patented technology

The present invention is directed to conjugated compounds comprising a folate, or an analog or derivative thereof, and an aziridinyl epothilone analog, as further described herein, and / or pharmaceutically-acceptable salts and / or solvates thereof, useful in the treatment of cancer or other folate-receptor associated conditions.

The present invention relates to methods for use in producing epothilones and analogs and derivatives thereof. A general method according to the present invention broadly comprises performing an aldol condensation of a first compound with a second compound thereby to form a third compound selected from the formulas: and stereoisomers thereof, and performing a macrolactonization of the third compound. The present invention also provides chemical compounds, and methods for producing such chemical compounds, that are useful in producing epothilones and analogs and derivatives thereof.

Biomarkers that are useful for identifying a mammal that will respond therapeutically or is responding therapeutically to a method of treating cancer that comprises administering a microtubule-stabilizing agent. In one aspect, the cancer is breast cancer, and the microtubule-stabilizing agent is an epothilone or analog or derivative thereof, or ixabepilone.

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect. The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect. The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

Formulations comprising one or more epothilones together with a pharmaceutically acceptable carrier, in particular such pharmaceutical compositions suitable for oral administration of an epothilone.

A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg / mL to about 0.9 mg / mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

The present invention provides compounds of formula (I): as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

Medical devices, compositions and methods to prevent or reduce restenosis using epothilones, geldanamycin analogs, and rapamycin or rapamycin analogs alone or in synergistic combinations.

The invention provides a process for producing Epothilones by utilizing Sorangium cellulosum, which comprises improving fermentation culture medium of Sorangium cellulosum, and charging cyclodextrins or cyclodextrin derivatives into the fermentation culture medium. The process can realize higher output of Epothilones production.

The invention discloses epothilone biosynthetic gene transcriptional regulation protein and a preparation method thereof. According to the epothilone biosynthetic gene transcriptional regulation protein and the preparation method thereof, a biotin-labeled epothilone biosynthetic gene promoter P3 fishing method is adopted for the first time to obtain the transcriptional regulation protein of an SOce M4 epothilone biosynthetic gene cluster, and the function of the transcriptional regulation protein is verified by adopting an EMSA experiment. The obtained novel epothilone biosynthetic gene cluster transcriptional regulation protein can lay a molecular biological foundation for the biosynthetic transcriptional regulation of sprangium cellulosum epothilone and the heterologous expression of the epothilone biosynthetic gene cluster, and therefore the efficient biosynthesis of the epothilone and the wide application of the epothilone in the aspect of biological medicine are promoted.

The present invention relates to the use of natural or synthetic Epothilones for the treatment prevention or alleviation of diseases caused by a dysbalance of osteoclast and osteoblast activity, especially osteoporosis.

Epothilone analogues include a molecular scaffold which holds at least one segment of epothilone in a predetermined orientation and which rigidities a region between the macrolactone ring and the aromatic side-chain.

The invention discloses a novel epothilone biosynthetic gene P3 promoter as well as a preparation method and application thereof. A nucleotide sequence of the P3 promoter is shown as SEQ ID NO. 1. Thepromoter of a So ce M4 epothilone biosynthetic gene is amplified by adopting a degenerate primer designing method for the first time; the promoter is subjected to cloning and promoter element analysis; and a luciferase reporter gene vector is adopted to verify the functions of the obtained epothilone biosynthetic gene promoter. The obtained novel epothilone biosynthetic gene cluster promoter canlay a molecular biological foundation for transcriptional regulation of sprangium cellulosum epothilone biosynthesis and heterologous expression of an epothilone biosynthetic gene cluster; the improvement of the yield of epothilone is promoted; and wide application of the epothilone in the aspect of biomedicines is promoted.

Epothilone resistant cells lines are disclosed. The invention also discloses methods for identifying substances which are cytotoxic to epothilone resistant cells or which are chemosensitizers or analogs of epothilone. The invention further discloses methods for identifying epothilone resistant cells and for inhibiting the growth of epothilone resistant cells in vitro and in vivo. The invention also discloses antibodies specific for epothilone resistant cells. Also disclosed is a method to identify microtubule stabilizing agents using the epothilone resistant cell lines disclosed.

The invention discloses an Epothilone freeze-dried compound which mainly contains the Epothilone, a solubilizer and a freeze-dried excipient; wherein, a preferable solubilizer is Carmowax 12-hydroxyl stearate. The product not only is simple in technique and is stable in quality, but also is low in side effect.

The invention discloses a method for increasing the fermentation yield of epothilone by using the metabolin of competitive microorganism namely rhizopus arrhizus or penicillium decumbens of sorangium cellulosum to induce. The method provided by the invention comprises the following steps of: cultivating the competitive microorganism, and extracting the metabolin of the competitive microorganism; adding the metabolin into a sorangium cellulosum fermentation medium, activating epothilone to produce related regulator genes inside the strain by using the stimulation of the external additive, and further stimulating the synthesis of epothilone. Detection results show that the fermentation yield of epothilone can be increased by 46.3-58.7% as compared with original conditions after the method is used, and the method has important theoretical significance and economic value.

The invention relates to a method for carrying out liposome modification on compound with free hydroxyl groups, in particular to liposome modified taxol and analogues thereof, as well as nanoparticlescontaining the liposome modified drug. According to the method disclosed by the invention, the taxol modified by liposome N,N'-di-dodecyl-L-glutamate diamide (LG-C12), 10-hydroxycamptothecine, irinotecan and epothilone B are specifically designed and successfully prepared, and the hydrophobicity of drugs is improved; then NH2-mPEG-DSPE bonded by mPEG-DSPE and mitochondrial targeted molecular triphenylphosphonium bromide (TPP) is utilized to coat liposome modified drugs to assemble into nanoparticles which improve the cytotoxic effect of the drugs on cancer cells and also reduce the toxic andside effects of the drugs on humans or animals.

An Aibomycine analog, its preparing process, its composite medicines, and its application for treating cancers and hyperplastic diseases and inducing apoptosis are disclosed.

The present invention concerns antibody-conjugate having general structure (2):AB-[(L6)-{Z-(L1)n-(L2)o-(L3)p-(L4)q-D}xx]yy   (2)wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The present invention relates to the use of natural or synthetic Epothilones for the treatment or prophylaxis of diseases caused by a dysbalance of osteoclast and osteoblast activity, especially osteoporosis.

The invention relates to an anti-tumor epothilone oral liquid. EpothiloneA-epothilonel are combined in different ways to generate different epothilone liquid mixtures; and the liquid mixtures are used as oral liquids since the epothilones are effective when being orally taken.

The present invention provides compounds of formula (I):as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

A method of treating a hyperproliferative disorder, including a cancer, in a subject in need of such treatment, comprising administering to said subject a pharmaceutical combination containing a treatment effective amount of: (a) a vitamin A derivative (i.e., a retinoid), or a pharmaceutically acceptable salt thereof, and an inhibitor of microtubule structure or function; or (b) a combination containing fenretinide (i.e., N-(4-hydrophenyl) retinamide, 4-HPR) and ABT-751 (i.e., N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide). Vitamin A derivatives that may be useful for this invention according to (a) include, but are not limited to, all-trans-retinoic acid, 13-cis-retinoic acid, and fenretinide. Microtubule inhibitors that may be useful for this invention according to (a) include, but are not limited to, inhibitors of the Vinca binding domain (e.g., vincristine, vinblastine, vinorelbine, and cryptophycin 52), inhibitors of the Taxane domain (e.g., paclitaxel, docetaxel, and epothilones), and inhibitors of the colchicine site (e.g., colchicine, ABT-751, CI-980, and combretastatin). A preferred retinoid according to (a) is fenretinide. A preferred microtubule inhibitor according to (b) is ABT-751.

The present invention provides compounds of formula (I):as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

Epothilone analogues include a molecular scaffold which holds at least one segment of epothilone in a predetermined orientation and which rigidities a region between the macrolactone ring and the aromatic side-chain.

The invention relates to an Epothilone analogue, a preparation method as well as a medicine composition and application thereof. Definitely, the invention relates to an analogue obtained by substituting a hydrogen in the C-9 position of Epothilone with methyl, a medicine composition as well as preparation method and application thereof, in particular to an Epothilone analogue medicine compound shown in a formula (I), a medicine composition containing effective amount of Epothilone analogue compound (I) and pharmaceutically acceptable carrier thereof and used for treating cancers or a composition of the Epothilone analogue compound and other anti-cancer medicines, a preparation method of the Epothilone analogue and application thereof in the medicines, especially the application in preparing medicaments for treating cancers, wherein the Epothilone analogue medicine compound is used for treating cancer diseases.

The invention discloses a method for heterologous expression of epothilone, wherein an epothilone gene cluster is introduced into a host strain while an epothilone precursor synthesis pathway is supplemented, and the introduction of a related tRNA gene and the insertion of a promoter are combined, such that the expression of epothilone can be substantially improved, wherein the yield is increasedby about 4 orders of magnitude, and can reach 8.5 mg / L. The present invention further provides a gene engineering strain capable of heterologous expression of epothilone, and an epothilone productionmethod.

A process for formulating certain epothilones and analogs thereof for parenteral administration is provided wherein the pH of the formulation for administration can be controlled to enhance the stability and thus, potency of the epothilone, or analog thereof.