124 results about "Hsp90" patented technology

Zearalanol compounds are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various disorders. Methods of synthesis and use of such compounds are also described and claimed.

The present invention concerns compositions comprising and methods of identification and use of targeting peptides selective for cancer tissue, particularly prostate or ovarian cancer tissue. The method may comprise identifying endogenous mimeotopes of such peptides, such as GRP78, IL-11Rα and hsp90. Antibodies against such targeting peptides or their mimeotopes may be used for detection, diagnosis and / or staging of prostate or ovarian cancer. In other embodiments, the compositions and methods concern novel type of gene therapy vector, known as adeno-associated phage (AAP). AAP are of use for targeted delivery of therapeutic agents to particular tissues, organs or cell types, such as prostate or ovarian cancer. In still other embodiments, targeting peptides selective for low-grade lipomas may be used for detection, diagnosis and targeted delivery of therapeutic agents.

The present invention provides novel methods of preparing triazole compounds which inhibit the activity of Hsp90. One embodiment of the invention is directed to methods for preparing a triazole compound represented by the following Structural Formula:or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising the steps of: a) reacting an amide represented by the following Structural Formula:with a thionation reagent to form a thioamide; b) reacting the thioamide of step a) with hydrazine to form a hydrazonamide; c) reacting the hydrazonamide of step b) with a carbonylation or a thiocarbonylation reagent.In one embodiment, the present invention is a method of synthesis of a compound of formula (IA)or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising reacting a compound of formula (IIA)with an oxidizing agent, thereby producing a compound of formula (IA).The present invention is also directed to a method of preparing a compound or a tautomer thereof represented by the following Structural Formula:or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof. The method comprises the step of reacting a first starting compound represented by the following Structural Formula:in the presence of a mercuric salt, with a second starting compound represented by the following Structural Formula:

The present invention describes inhibitors of extracellular Hsp90. The inhibition of extracellular Hsp90 leads to a reduction of the invasiveness of the tumor cells. Furthermore, the invention relates to the use of molecules inhibiting extracellular Hsp90 function for the manufacture of a medicament for the treatment or prevention of invasion and / or metastatic potential of cancer cells.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

The present invention relates to substituted pyrrole compounds and compositions comprising substituted pyrrole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted pyrrole compound of the invention, or a pharmaceutical composition comprising such a compound.

The invention provides compositions and methods to determine or detect the activity of enzymes, including phosphotransferases such as kinases (e.g., protein, lipid, and sugar kinases) and ATP hydrolases such as ATPases, e.g., HSP90, that employ ATP as a substrate and form ADP as a product by monitoring changes in ADP.

The present disclosure provides a series of compounds which exhibit isoform selective inhibition of GRP94, a homologue of Hsp90 that is localized to the endoplasmic recticulum. Through GRP94 inhibition, these compounds are likely to manifest anti-cancer, anti-inflammatory, anti-metastasis, and immunosuppressive activities, as well as utility in the treatment of neurodegenerative diseases, and diabetes.

The invention provides an acid addition salt of a compound of the formula (1) Also provided by the invention are processes for preparing the compound of formula (1) and alkyl analogues thereof, novel intermediates for use in the process and methods for preparing the intermediates. The invention also provides new medical uses of compounds of the formula (1) and its ethyl analogue.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.

The invention discloses a triazole derivative having an HSP90 (Heat Shock Protein) inhibiting activity, as well as a preparation method and an application of the triazole derivative. Specifically, the invention relates to the triazole derivative having a structure as shown in a formula (I), a stereisomer of the triazole derivative and a pharmaceutically acceptable salt, wherein the definition of each substituent group in the formula (I) and the definition in a description are the same. The compound with a novel structure has the HSP90 inhibiting activity, can be used to cure cancers, neurodegenerative disorders, inflammation diseases, autoimmune diseases, ischemic brain injuries and the like, and has a broad application prospect.

Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

The present invention describes the inhibitors of extracellular Hsp90. The inhibition of extracellular Hsp90 leads to a reduction of the invasiveness of the tumor cells. Furthermore, the invention relates to the use of molecules inhibiting extracellular Hsp90 function for the manufacture of a medicament for the treatment or prevention of invasion and / or metastatic potential of cancer cells.

The invention discloses a screening method of brown planthopper reference genes under high temperature stress. According to the screening method, fluorescent quantitative PCR studies are carried out through taking brown planthopper under no stress as a control material and brown planthoppers under the stress of different high temperatures as experimental materials; and quantitative PCR data of candidate reference genes are input to geNorm and BestKeeper softwares to be analyzed so as to screen the most suitable and most stably expressive reference gene-actin1 in the brown planthoppers under the high temperature stress and under no stress. On the basis, the expression pattern of an hsp90 gene of the brown planthopper under the high temperature stress is studied by the inventor through taking the brown planthopper at the high temperature as a sample, the heat shock protein gene hsp90 of the brown planthopper as a target gene and the screened actin1gene as the reference gene.

The invention provides a compound which is (a) a phenylamide derivative of formula (I) or a tautomer thereof, or (b) a pharmaceutically acceptable salt, N-oxide, hydrate, prodrug or solvate thereof: wherein R1, R2, R3, R4, R5, R6 and R7 are as defined herein. The compounds are useful in the treatment of diseases mediated by HSP90.

Methods of treating cancer with a compound of formula (I) are disclosed. Also provided are methods of treating a cancer with a KRAS mutation or an ALK+ cancer with a compound of formula (I). Further provided are methods of treating KRAS− mutated or ALK+ NSCLC with a compound of formula (I):

The invention discloses an application of 3,5-(E)-diarylmethylene-N-cyclopropyl piperidin-4-one compounds as an Hsp90 depressant. The invention discloses use of the 3,5-(E)-diarylmethylene-N-cyclopropyl piperidin-4-one compounds 1-4 represented by formulae shown in the description and compositions thereof in preparation of drugs for treating or preventing Hsp90 induced diseases. According to the use disclosed by the invention, the Hsp90 induced diseases are leukemia, colon cancer, liver cancer, lymphoma, nasopharyngeal carcinoma or breast cancer. According to the application, the compounds have powerful Hsp90 depression activity, and in vitro, the depression activity of the compounds 1-4 to six kinds of tumor cells is higher than that of 2F by 2 to 20 times. In vivo, relatively high nude-mouse transplantation tumor propagation depression activity is shown, so that the compounds can be used for preparing drugs for treating the leukemia, the colon cancer, the liver cancer, the lymphoma, the nasopharyngeal carcinoma and the breast cancer.

The present invention relates to formula I compounds having antitumoural activities through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical compositions containing such compounds.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. The molecular profiling can be used to provide a diagnosis, prognosis, or theranosis for the disease, such as identifying a candidate treatment. The methods can detect expression levels of SPARC and HSP90. The cancer can be, e.g., a renal cell carcinoma or an interdigitating dendritic cell sarcoma.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a pharmaceutical composition comprising such a compound.