182 results about "P-gp inhibitor" patented technology

Compounds which are otherwise difficult to solubilize, such as, for example, pharmaceutical actives difficult for the body to absorb, are solubilized into a composition using a solvent system that is a structured fluid. The structured fluid is a reversed cubic phase or reversed hexagonal phase material, or a combination thereof, which includes a polar solvent, a surfactant and a non-paraffinic liquid with a high octanol-water partition coefficient which does not qualify as a surfactant. The compositions thus formed are able to enhance absorption of drugs by the induction of local, transient nanopores in biomembrane absorption barriers and particularly those in which efflux mechanisms, such as those associated with P-glycoprotein and / or cytochrome 3A4, are active. The compositions and methods that are used for solubilizing pharmaceutical actives in structured fluids can simultaneously accomplish solubilization of difficultly soluble drugs and enhancement of absorption.

The present invention relates to a method of enhancing the bioavailability of a piperidinoalkanol antihistamine in a patient which comprises co-administering to said patient an effective antihistaminic amount of said piperidinoalkanol and an effective p-glycoprotein inhibiting amount of a p-glycoprotein inhibitor.

This invention relates to compounds, compositions, and methods useful for modulating MDR P-glycoprotein (MDR) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MDR gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MDR genes.

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

The present invention relates to efflux inhibitor compositions and methods of using these agents for treating conditions where the activity of efflux transporter proteins (e.g., Breast Cancer Resistance Protein (BCRP) and P-Glycoprotein (P-GP)) inhibit effective delivery of a therapeutic agent to a target tissue (e.g., brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, and / or stem cells).

A method for inhibiting therapeutic drug resistance within a cell over-expressing a membrane protein is provided. The method comprises synthesizing a dimeric prodrug inhibitor of a monomeric therapeutic agent; administering the dimeric prodrug inhibitor to the membrane protein together with the monomeric therapeutic agent; and occupying at least one substrate binding site of the membrane protein with the synthesized dimeric prodrug to allow the monomeric therapeutic agent to accumulate within the cell. The dimeric prodrug inhibitor contains a crosslinking agent that is adapted to breakdown under reducing conditions within the cytosol of the cell to cause the dimeric prodrug to revert back to a form equivalent to the monomeric therapeutic agent.

The invention encompasses neutral dithiocarbamate metal compounds and methods of treating cancer using such compounds, along with methods for sensitizing AIDS / HIV patients to anti-retroviral therapy by blocking the P-glycoprotein membrane toxin extrusion pump using such compounds. Compounds inhibit the growth of cancer cells of a variety of cell types. A method is presented for using the neutral compounds disclosed herein, amongst other uses disclosed herein, to reduce tumor growth, and to potentiate the effect of other anticancer agents. The invention also encompasses pharmaceutical compositions comprising the neutral compounds and a pharmaceutically acceptable excipient, diluent, solubilizer, solvent, adjuvant or carrier, or a mixture thereof.

The invention discloses preparation and application of an insoluble drug-entrapped poloxamer / amphiphilic polysaccharide mixed micelle. The insoluble drug-entrapped poloxamer / amphiphilic polysaccharide mixed micelle is prepared through a dialysis method or a solvent evaporation method. The mixed micelle is low in critical micelle concentration, is high in drug-loading rate, is capable of obviously prolonging the stabilization time and has the long-circulation function of a nanomicelle and has dual functions of restraining the metabolism of P-glycoprotein and cytochrome P450 enzyme and is capable of increasing the bioavailability of oral administration. The mixed micelle is simple in preparation method, is mature in process and is high in yield and can be prepared into preparations for the oral administration, such as tablets, capsules, pills and syrups.

The invention relates to a new class of compounds, which are 1-phenylalcoxy-2-β-phenylethyl derivatives, as P-glycoprotein (P-GP) inhibitors. These compounds are useful in drug resistance events. They have been shown able to inhibit in a dose-dependent manner Glycoprotein-P (P-gp) activity in cell lines in which the expression of said glycoprotein is very high, like Caco-2 (human colon cancer) cells and MCF7 / Adr (adriamycin-resistant human breast carcinoma) cells. The invention also relates to methods of production and the utilization of such compounds as medicaments useful in the treatment of states linked to the difficulty for some drugs to cross the blood-brain barrier (BBB) and generally within the context of the problems of drug resistance induced by chemotherapy agents.

The invention relates to an MDR family P-glycoprotein located on human chromosome 7p15-21, polynucleotide sequences encoding this P-glycoprotein and fragments thereof. This gene is utilized in methods for assessing cancer cell susceptibility to therapies directed against multidrug resistance, and for the design of diagnostic and therapeutic methods relating to cancer multidrug resistance. The invention also relates to methods for determining whether a test compound may inhibit multidrug resistance.

The present invention is directed to polypeptides (e.g., fragments) derived from P-glycoprotein and caveolin-1 which are capable of inhibiting the interaction between these two proteins. Inhibition of this interaction leads to increase of efflux of compounds that are transported by P-gp. The invention further includes methods of treating patients having diseases that benefit from increased P-gp-mediated efflux. Such diseases include neoplasms such as cancer and neurological diseases such as neurodegenerative diseases.

The present invention concerns medical products that release pharmaceutically active substances, the efficiency of which is increased as the result of a combination with an inhibitor of the transport protein P-glycoprotein.

The invention relates to protein-protein interactions and methods for identifying interacting proteins and the amino acid sequence at the site of interaction. Using overlapping hexapeptides that encode for the entire amino acid sequences of the linker domains of human P-glycoprotein gene 1 and 3 (HP-gp1 and HP-gp3), a direct and specific binding between HP-gp1 and 3 linker domains and intracellular proteins was demonstrated. Three different stretches (617EKGIYFKLVTM627, (SEQ ID NO: 1) 658SRSSLIRKRSTRRSVRGSQA677 (SEQ ID NO: 2) and 694PVSFWRIMKLNLT706 (SEQ ID NO: 3) for HP-gp1 and 618LMKKEGVYFKLVNM631 (SEQ ID NO: 4), 648KAATRMAPNGWKSRLFRHSTQKNLKNS674 (SEQ ID NO: 5), and 695PVSFLKVLKLNKT707 (SEQ ID NO: 6) for HP-gp3) in linker domains bound to proteins with apparent molecular masses of ˜80 kDa, 57 kDa and 30 kDa. The binding of the 57 kDa protein was further characterized. Purification and partial N-terminal amino acid sequencing of the 57 kDa protein showed that it encodes the N-terminal amino acids of alpha and beta-tubulins. The method of the present invention was further validated with Annexin. The present invention thus demonstrates a novel concept whereby the interactions between two proteins are mediated by strings of few amino acids with high and repulsive binding energies, enabling the identification of high affinity binding sites between any interacting proteins.

The present invention is directed to purified preparations of dermal mesenchymal stem cells that are characterized by the cell surface expression of the ABCB5 P-glycoprotein. The cells may be used for any purpose that mesenchymal stem cells from other course are used. For instance,they may be administered to treat an organ transplant recipient to improve allograft survival or as a treatment to patients with autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.

The present invention describes the use of polysaccharides, surfactants, and dendrimers as bioavailability enhancers for oral pharmaceutical compositions. These substances exhert an inhibitory action of the gastrointestinal pump efflux proteins, such as the P-glycoprotein and the MDR protein, responsible for poor drug bioavailability and multidrug resistance. The formulations herein described comprise a medicinally active substance in association with said polysaccharides, surfactants, and dendrimers. They are well tolerated, are not absorbed by the gastrointestinal tract, and increase the bioavailability and the activity of orally administered medicaments, like, e.g. antineoplastic, antiviral, antibiotic, or antidepressant medicaments.

The invention discloses a 23-hydroxy betulinic acid derivative as well as a preparation method and application thereof. The derivative has a structure as shown in a formula (I). The 23-hydroxy betulinic acid derivative can be used for resisting tumors and used as a tumor medicament resistance reversal agent. The 23-hydroxy betulinic acid derivative can be used for effectively inhibiting the proliferation of tumor cells and also can be used for obviously increasing the antipersonnel force of DOX (doxorubicin) on a P-glycoprotein overexpression cell strain HepG2 / ADM under the condition of non-toxicity dosage.

The present invention relates to a method of determining P-glycoprotein expression and / or function for a patient with solid tumors, leukemias, and other malignancies. The invention also relates to using a P-glycoprotein expression and / or function diagnostic in conjunction with methods for treating solid tumors, leukemias, and other malignancies with a chemotherapeutic agent in combination with zosuquidar. The methods are particularly effective in treating acute myelogenous leukemia, metastatic breast cancer, and other cancers expressing P-glycoprotein, wherein the P-glycoprotein expression and / or function is used to select a treatment option for the patient.

The invention relates to a tree-like polymer nanometer drug delivery carrier targeting doxorubicin. The structural general formula of the targeting doxorubicin is PEG-b-PAMAM-hydrozone-(DOX)n. A tree-like polymer nanometer drug delivery carrier targeting doxorubicin of liquid tumors representative to myeloma is provided in the invention. The acidic environment (pH of 5.5) of myeloma makes a hydrogen bond connecting a carrier with doxorubicin be broken, so complete doxorubicin molecules are released. The release is only carried out under the acidic condition of the myeloma, so the treatment pertinence of the drug is greatly improved. P-glycoprotein will diffuse to doxorubicin monomer elimination cells in cells, so tumor cells generate multiple drug resistances. The carrier drug can avoid the medicine efflux phenomenon caused by the p-glycoprotein and can also avoid the multiple drug resistances.

The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.

Systems and methods are provided for detecting and quantitating one or more compounds or molecules in a sample. An aptamer-based point-of-care device (such as a strip) is described for rapid detection of target molecules such as the cancer marker p-glycoprotein (Pgp). Fluorescent molecules or gold nanoparticles may be used to detect the binding between a target molecule and the aptamer. By way of example, fluorescence resonance energy transfer (FRET) or Dynamic Light Scattering (DLS) may be used for detecting the physical and / or chemical changes caused by the binding of the aptamers to the target molecules.

The invention relates to an antineoplastic prodrug with a P-glycoprotein inhibition function. The antineoplastic prodrug is an amphiphilic substance formed by connecting antineoplastic drugs and chitosan-polyethlyene glycols-succinate with the P-glycoprotein inhibition function through a connector in a covalent mode. The connector comprises a sensitive bond and at least two reaction functional groups respectively used for connecting the antineoplastic drugs and the chitosan-polyethlyene glycols-succinate in a covalent mode, wherein the sensitive bond is a chemical bond which is easily broken under a reducing environment or an acid environment in a tumor cell. The antineoplastic prodrug with the P-glycoprotein inhibition function is expected to effectively treat tumors and drug-fast tumors.

This invention is directed to methods of inhibiting coagulation or treating thrombosis using a factor Xa inhibitor and a P-glycoprotein (Pgp) inhibitor. The invention is also directed to formulations used in the methods.

The invention relates to the genetic modification of plants, particularly to the expression of P-glycoprotein genes in transformed plants. Nucleotide sequences for the Br2 gene encoding a P-glycoprotein of maize and methods for their use are provided. The sequences find use in modifying the growth of plants.

Methods of application of Schisandrin B in the preparation of anticancer medications, and particularly for the preparation of medications for the treatment of multidrug resistant (MDR) cancer. The compound of Schisandrin B effectively reverses MDR cancer in combination with other anticancer chemotherapeutic agents. Schisandrin B reverses MDR cancer by inhibiting the drug efflux activity of P-glycoprotein, indicating its significance in clinical applications. Although it is of low toxicity, Schisandrin B is cytotoxic to human cancer cells, revealing its application in cancer chemotherapy. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

Provided are Breast Cancer Resistance Protein (BCRP) inhibitors, P-glycoprotein (P-gp) inhibitors and chemotherapeutic agents for use in the treatment of cancer by combination therapy of the BCRP inhibitor and / or P-gp inhibitor with the chemotherapeutic agent. The chemotherapeutic agent is an imidazotetrazine, e.g. temozolomide.

The present invention provides substituted pyrrolo-, furano-, and cyclopentylpyrimidine bicyclic compounds of formula III,and 5,6-saturated and unsaturatedand pharmaceutically acceptable salts, prodrugs, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.