11 results about "Vorinostat" patented technology

The present invention relates to the early treatment, including pre-diagnosis treatment, of sepsis and acute inflammatory syndromes such as systemic inflammatory response syndrome (SIRS) by PLA2 and metalloprotease inhibitors to improve the performance of antibiotics and outcomes prior to and after confirmation of the diagnosis of sepsis and / or SIRS in a patient or subject. Additional embodiments include methods of treating sepsis, anthrax and severe acute respiratory syndrome coronavirus (SARS and SARS-CoV2) and related inflammatory syndromes and compositions, including pharmaceutical compositions and blood sample compositions. In further embodiments, the present invention is directed to embodiments which evidence that LY315920, LY333013 and related sPLA2 inhibitors are particularly effective COVID-19 / cytokine release syndrome therapeutics-prophylactics. In embodiments, the PLA2 inhibitor is varespladib (LY315920), methyl varespladib (LY333013), AZD2716-(R)-3-(5′-benzyl-2′-carbamoyl-[1,1′-biphenyl]-3-yl)-2-methylpropanoic acid—as a racemic mixture or separately, as the “R” enantiomer), compound 4 (3-(5′-benzyl-2′-carbamoyl-[1,1′-biphenyl]-3-yl)-propanoic acid) and LY433771 ((9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl) oxyacetic acid), a pharmaceutically acceptable salt thereof or a mixture thereof. In embodiments, the metalloprotease inhibitor is Prinomastat, Batimastat, marimastat or vorinostat dosed alone or in combination with preferred sPLA2 inhibitors for the treatment of infection, inflammatory and wound conditions arising from various causes. Methods and compositions for achieving accelerated treatment of wounds and burns, anthrax metalloprotease toxin (lethal factor) driven complications, ARDS, neo-natal and pediatric acute respiratory distress syndrome (neo-natal / pediatric ARDS), including meconium aspiration syndrome and other disease states and conditions are also disclosed.

The invention provides an application of an HDAH inhibitor in preparation of antibiotics. According to the invention, research finds that escherichia coli has Zn < 2 + >-dependent histone deacetylase-like amide hydrolase-HDAH, and the HDAH can directly influence the enzyme activity of metabolic enzyme through acetylation modification so as to regulate and control the metabolic level of bacteria; and the transcription level of metabolism-related genes can be indirectly regulated by acting on a transcription regulation factor (such as histone-like protein HU), and the metabolism of escherichia coli is synergistically regulated from two levels of post-translational modification and transcription. The invention also finds that the vorinostat (SAHA), the trichosaliocin (TSA) and the like can be combined with the HDAH and inhibit the deacetylation activity of the HDAH, are HDAH inhibitors, and inhibit the growth and migration ability of escherichia coli after being administered to the escherichia coli.

The subject invention provides methods for synthesizing suberoylanilide hydroxamic acid (SAHA) and precursors thereof. These methods involve novel synthetic scheme for SAHA which eliminate purification of intermediates, and produce SAHA product in high purity and high yield, making them suitable for scale-up and GMP manufacturing of SAHA.

The invention belongs to the technical field of biological medicines, and provides phthalazinone or quinazolinone derivatives as well as a preparation method and application thereof. The phthalazinone or quinazolinone derivative, the stereoisomer thereof, the optical isomer thereof or the pharmaceutically acceptable salt thereof provided by the invention can play an anti-tumor role by inhibiting histone deacetylase, and all have good in-vitro anti-tumor activity; even, the compound has the effect equivalent to or better than that of an anti-cancer drug SAHA (vorinostat) of a positive control group, and targeted tumor resistance can be realized.

This invention discloses a method for real-time monitoring of the inhibitory effect of a small molecule drug, vorinostat, comprising the following steps: constructing a fluorescence confocal electrochemical impedance microscopy imaging system using a WS2 chip as the working electrode; immobilizing probe protein molecules on the surface of the WS2 chip; applying an electrical signal to the WS2 chip after probe protein molecule immobilization, and monitoring the inhibitory effect of the small molecule drug by the change curve of the amplitude signal over time. In this invention, when the small molecule drug binds to the probe protein molecules immobilized on the WS2 surface, the surface charge of the WS2 changes, and the inhibitory effect of the small molecule drug on the probe protein molecules is monitored by the change of the WS2 fluorescence signal.

The invention belongs to the field of cell biology, and particularly relates to a volmetinib-resistant non-small cell lung cancer cell strain HCC827 / FR and application thereof. The preservation number of the non-small cell lung cancer cell strain HCC827 / FR resistant to the vomitinib is CCTCC (China Center For Type Culture Collection) NO: C202583; the 19 exon of the volmetinib-resistant non-small cell lung cancer cell strain HCC827 / FR is subjected to deletion mutation; the drug-resistant gene of the non-small cell lung cancer cell strain HCC827 / FR resistant to the vomitinib is IGFBP7 (insulin-like growth factor binding protein 7). The vomitinib-resistant non-small cell lung cancer cell strain HCC827 / FR provided by the invention can be used for researching a vomitinib drug-resistant mechanism, constructing an in-vivo and in-vitro drug-resistant tumor model, screening an anti-tumor drug, evaluating drug sensitivity, developing a drug-resistant reversal drug based on an IGFBP7 gene, and researching a phenotype transformation mechanism from non-small cell lung cancer to small cell lung cancer after EGFR-TKI treatment.

The subject invention provides methods for synthesizing suberoylanilide hydroxamic acid (SAHA) and precursors thereof. These methods involve novel synthetic scheme for SAHA which eliminate purification of intermediates, and produce SAHA product in high purity and high yield, making them suitable for scale-up and GMP manufacturing of SAHA.

The invention belongs to the technical field of biological medicines, and discloses an immunoregulation method for directional differentiation of CD4 + T cells. According to the method, an intelligent response type three-dimensional support composed of a temperature-sensitive block copolymer, MMP degradable peptide and a pH-sensitive component is constructed, a space-time nest is formed in situ at a focus, three active molecules including vorinostat, IL-6 / rapamycin and TGF-beta1 / retinoic acid are loaded by adopting a layered drug loading strategy, dynamic release is performed according to a microenvironment, and the pH-sensitive drug-loaded vorinostat / IL-6 / rapamycin / TGF-beta1 / retinoic acid is obtained. The efficient, lasting and antigen-specific directional induction of CD4 + T cells to subgroups such as Treg or Th17 is realized. The method is not only suitable for various disease scenes such as tumors, autoimmune diseases and chronic inflammation, but also can flexibly adapt to different T cell subpopulation induction requirements by replacing loaded bioactive molecule combinations and antigen peptide sequences, the local T cell regulation efficiency can be remarkably improved, systemic toxicity is avoided, and the method is suitable for clinical application. And good biocompatibility and clinical transformation potential are achieved.

The invention provides a method for detecting genotoxic impurities in a Vonoprazan fumarate preparation, the genotoxic impurities are pyridine ring N-oxides, and the structure of the genotoxic impurities is shown as a formula I. The invention further provides a method for detecting the genotoxic impurities in the Vonoprazan fumarate preparation. The detection method comprises the following steps: mixing a to-be-detected sample with an extraction solvent, performing vortex, performing centrifugation, performing filtration, taking a subsequent filtrate, and performing dilution so as to obtain a test solution; mixing an impurity reference substance with an acetonitrile aqueous solution to obtain a reference substance solution; and performing high performance liquid chromatography detection on the test solution and the reference solution, and determining the content of the genotoxic impurities according to a detection result. The method provided by the invention has the advantages of short peak appearance time, beautiful peak shape, good separation degree, high sensitivity, high accuracy, good durability and the like, is low in quantitation limit and detection limit, can rapidly and effectively detect trace potential genotoxic oxidation impurities in the Vonoprasone fumarate tablets, can efficiently realize quantitative analysis of the oxidation impurities, and has a wide application prospect. The method has important practical significance on the quality control of the fumaric acid Vonoprazan tablets.

The invention discloses epigenetic / copper death synergistic nanoparticles as well as a preparation method and application thereof, and belongs to the technical field of nano-drug delivery systems. The nanoparticle is specifically a vorinostat-calcium carbonate nanoparticle coated with a dihydromyricetin-copper metal phenolic network, the calcium carbonate nanoparticle loaded with vorinostat (SAHA) is prepared through a gas diffusion method, the surface of the calcium carbonate nanoparticle is coated with the dihydromyricetin-copper (DMY-Cu) metal phenolic network, and the SAHA-CaCO3 (at) DMY-Cu nanoparticle is prepared. The SAHA-CaCO3 (at) DMY-Cu nanoparticles prepared by the invention are stable in structure under physiological conditions, can release SAHA, DMY and Cu < 2 + > in a tumor microenvironment, synchronously realize epigenetic regulation and copper death induction, remarkably kill tumor cells and remodel an immune microenvironment, show excellent treatment effect and biological safety on malignant tumors, and have wide application prospects.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing Vonoprazan as well as a preparation method and application of the pharmaceutical composition. The composition contains the 15-hydroxystearic acid polyethylene glycol ester and the polycarbophil, so that the stability of the fumarate vonorbitan tablet in the preparation and storage processes is effectively ensured; through investigation under the conditions of high temperature, illumination and acceleration, the product has good stability, especially the drug does not contain N-nitrosovonoprazan, and the safety of the fumaric acid vonoprazan tablet is improved.