50 results about "Plinabulin" patented technology

Disclosed herein are methods of treating a cancer characterized by expressing a mutant form of a RAS protein. Some embodiments relate to treatment of cancer by administering Plinabulin to a subject in need thereof.

Disclosed herein are methods of treating a brain tumor by administering Plinabulin. Some embodiments relate to treatment of glioblastoma multiforme by administering Plinabulin.

Disclosed herein are plinabulin and the use for reducing neutropenia. Some embodiments relate to reducing the docetaxel induced neutropenia using plinabulin.

Disclosed herein are methods of treating a brain tumor by administering Plinabulin. Some embodiments relate to treatment of glioblastoma multiforme by administering Plinabulin.

This invention provides a novel cancer treatment method in which plinabulin (t-butyl-dehydrophenylahistin or NPI-2358) and a taxane compound (such as docetaxel) are used in combination. Our study has shown that the optimum combination of injecting plinabulin after taxane compound has unexpected enhanced efficacy in large tumor populations in animal model and in NSCLC cancer patients compared to taxane compound treatment alone. In addition, this optimum combination can achieve unexpected safety effect in lowering unbearable side effects of taxane compound, including decreasing its neutropenia rates at all grades and decreasing G-CSF use in cancer patients.

This invention provides a novel cancer treatment method in which plinabulin (t-butyl-dehydrophenylahistin or NPI-2358) and a taxane compound (such as docetaxel) are used in combination. Our study has shown that the optimum combination of injecting plinabulin after taxane compound has unexpected enhanced efficacy in large tumor populations in animal model and in NSCLC cancer patients compared to taxane compound treatment alone. In addition, this optimum combination can achieve unexpected safety effect in lowering unbearable side effects of taxane compound, including decreasing its neutropenia rates at all grades and decreasing G-CSF use in cancer patients.

Disclosed herein are methods of treating a cancer characterized by expressing a mutant form of a RAS protein. Some embodiments relate to treatment of cancer by administering Plinabulin to a subject in need thereof.

The invention provides polymorphism of a deuterium-substituted plinabulin compound and a preparation method and application of the polymorphism, specifically polymorphism of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) deuterium-substituted methylene)piperazidine-2,5-diketone and preparation method and application of the polymorphism. Based on (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) deuterium-substituted methylene)piperazidine-2,5-diketone, the polymorphism of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) deuterium-substituted methylene)piperazidine-2,5-diketone is researched, and alpha, beta, gamma, delta, and epsilon crystal forms are found. The polymorphism and preparation method and application are of great significance on research of pharmaceutical polymorphism and screening of a crystal form with excellent pharmaceutical effect, and alpha, beta, gamma, delta, and epsilon crystal forms are fully developed and applied with respect to curative effect and dosage form selection of antitumor drugs.

Disclosed herein are compositions including a compound of formula (I) for treating cancer. Some embodiments relate to methods of treating cancer by co-administering a compound of formula (I) and one or more immune checkpoint inhibitor to a subject in need thereof. Some embodiments relate to methods of treating cancer by co-administering a compound of formula (I) and plinabulin to a subject in need thereof. Some embodiments relate to methods of providing co-stimulation of T-cell activation against cancer by co-administering a compound of formula (I), one or more immune checkpoint inhibitor.

Disclosed herein are methods of reducing neutropenia that is caused by chemotherapy or radiation therapy by administering plinabulin to a subject.

Plinabulin and one or more G-CSF drugs are used for treating a chemotherapy induced neutropenia, stimulating neutrophil survival, reducing bone pain induced by the G-CSF drug and alleviating immune suppression effect induced by the G-CSF drug. For example, docetaxel-induced neutropenia can be reduced by-co-administering plinabulin and one or more G-CSF compounds.

Disclosed herein are methods of reducing or preventing thrombocytopenia, in a clinically relevant manner, that is caused by chemotherapy or radiation therapy by administering plinabulin to a subject.

The invention provides a preparation and purification method of high-purity Plinabulin compound, which aims at mainly removing a trans-isomer. The preparation and purification method has the advantages that (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)methylene)piperazine-2,5-diketone monohydrate and (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuterated methylene)piperazine-2,5-diketone monohydrate are prepared; the purity of the prepared product is higher than 99.5%, and the content of the trans-isomer is smaller than 0.1%. The invention also relates to the preparation and purification of important intermediates, such as 5-(tert-butyl)-1H-imidazole-4-ethyl formate and 1,4-diacetylpiperazine-2,5-diketone. The preparation and purification method has the advantages that the production cost is reduced, the pos-treatment difficulty is decreased, and the technology more meets the requirements of industrialized production.

The invention discloses a preparation method and application of a tubulin inhibitor plinabulin isomer impurity, and belongs to the technical field of medicinal chemistry. (3Z, 6Z)-3-[(5-tert-butyl-1H-imidazole-4-yl) methylene]-6-(benzylidene)-2, 5-piperazinedione is subjected to illumination, and after the reaction reaches equilibrium, a mixed solvent is recrystallized and purified to obtain the impurity with the 6Z-to-6E configuration. The impurity is very key in quality research on preparation of a medicine plinabulin for treating and resisting tumor diseases and neutropenia, and can be used as an impurity reference substance based on related characteristics of the impurity.

This invention relates to use of neuropilin-2 as a novel biomarker and therapeutic target for melanoma. The presence of neuropilin-2 can be used as a biomarker for diagnosing and detecting individuals suffering from or at risk for developing melanoma. Also described are methods of using neuropilin-2 to capture circulating melanoma cells. The present invention further relates to methods of treating an individual suffering from or at risk for developing melanoma with an agent that inhibits the activity of neuropilin-2.

Disclosed herein are methods of reducing neutropenia that is caused by chemotherapy or radiation therapy by administering plinabulin to a subject.

The invention provides a plinabulin compound polycrystalline type and a preparation method thereof, and particularly relates to a polycrystalline type of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone and a preparation method thereof. Three kinds of crystalline types beta, gamma and delta are developed on the basis of the crystalline type alpha of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone, wherein the three kinds of crystalline types beta, gamma and delta can be prepared into monocrystallines; the three kinds of crystalline types have the advantages of clear conformation, high purity and high method repeatability; the important significance is realized on implementation of plinabulin biological effectiveness study and dosage form variety development.

Disclosed herein are compositions and methods for treating cancer, specifically extensive-stage small-cell lung cancer (ES-SCLC), through the administration of a combination therapy. In some embodiments, the method comprises administering plinabulin, one or more immune checkpoint inhibitors, including but not limited to pembrolizumab, and a regimen of etoposide with a platinum-based agent (EP). The disclosed methods enhance tumor reduction, prolong progression-free survival, and improve overall treatment efficacy compared to traditional therapies.

Disclosed herein are methods of reducing neutropenia that is caused by chemotherapy or radiation therapy by administering plinabulin to a subject.

Disclosed herein are methods of treating cancer by administering plinabulin and a cyclin-dependent kinase inhibitor, such as abamecril, in combination.

The invention relates to the technical field of cancer chemotherapy drugs, and discloses a pharmaceutical composition containing plinabulin and application thereof. The active ingredients of the pharmaceutical composition comprise plinabulin and tetrandrine. Various malignant tumor cells can be inhibited and killed through combination of tetrandrine and plinabulin, the dosage can be reduced, the treatment cycle can be shortened, toxic and side effects can be reduced, and adverse reactions caused by the toxic and side effects are reduced accordingly. A new choice is provided in the aspect of avoiding drug resistance or medicine resistance.

The invention relates to a T-peptide immunomodulator for treating sepsis. The immunomodulator adopts the structure of (Thr-Lys-Pro-Arg-AAN)4-(Lys-AAN)2-Lys-AAN, wherein N is a natural number. According to the immunomodulator, through animal experiment researches, the fact that T-peptide has functions of modulating proliferation and secretion of effector T cells and can relieve the negative immunoregulationeffect of regulatory T cells through combination of Nrp-1 (neuropilin-1) of surface molecules of the regulatory T cells is discovered. The T-peptide can relieve the immunosuppression state caused by the sepsis through the mechanism, particularly the cellular immunosuppression, so that the survival rate of sepsis mice can be increased, sepsis symptoms can be improved, and the T-peptide immunomodulator can be used for treating the sepsis.

Disclosed herein are plinabulin and its use for treating a cancer or tumor characterized by expression of a mutant form of an epidermal growth factor receptor (EGFR) protein, comprising administering plinabulin to a subject in need thereof.

The invention provides a detection and analysis method of plinabulin and related impurities thereof. The detection and analysis method comprises the following steps: (1) preparing a to-be-detected sample solution; the sample to be detected is a chemical product containing plinabulin and / or related impurities thereof; and (2) detecting the to-be-detected sample solution by adopting high performance liquid chromatography, wherein the detection conditions are as follows: a, a chromatographic column: filling a C18 bonded silica gel chromatographic column resistant to a high-proportion water phase; the mobile phase is composed of a mobile phase A and a mobile phase B, the mobile phase A is a monopotassium phosphate buffer solution, and the mobile phase B is acetonitrile; c, the flow rate is 0.6 ml / min; and d, the detection wavelength is selected from 200 to 320 nm. According to the method, the separation of plinabulin from various related impurities can be realized.

Disclosed herein are treatment of cancer by combined administration of plinabulin and an immune checkpoint inhibitor.

The present invention provides a salt crystal form of plinabulin. Specifically, the present invention provides a salt crystal form of a compound as represented by formula I. The salt crystal form of the present invention has excellent solubility, hygroscopicity and pharmacokinetic properties.

Disclosed herein are methods of reducing, preventing or ameliorating tissue iron excess and iron disorders associated with plasma haptoglobin consumption / reduction in the event of increased plasma hemoglobin levels due to hemolysis. In particular, some embodiments relate to administering to a subject a clinically related amount of plinabulin.

Disclosed herein are compositions and methods for treating diseases in need of enhanced immunogenicity. Some embodiments provided herein relate to compositions comprising a T cell activator and / or proliferative agent, one or more immune checkpoint inhibitors, and an FPPS inhibitor. Some embodiments relate to methods of treating cancer by co-administering plinabulin, one or more immune checkpoint inhibitors, and an FPPS inhibitor to a subject in need thereof.

The present invention discloses halimide and plinabulin and structural analogues and their use in the treatment and prevention in epilepsy and other seizures. The present invention further discloses methods to screen halimide-like molecules as pharmaceutically active compounds.

The invention provides a salt crystal form of plinabulin. Specifically, the invention provides a salt crystal form of a compound shown as a formula I. The salt crystal form provided by the invention has excellent solubility, hygroscopicity and pharmacokinetic performance.