46 results about "Staurosporine" patented technology

Methods of stimulating an immune response and treating patients responsive thereto with 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-diones, staurosporine analogs, derivatized pyridazines, chromen-4-ones, indolinones, quinazolines, nucleoside analogs, and other small molecules are disclosed. In a preferred embodiment benzopyrimidine derivatives such as ZD-6474, MLN-518, lapatinib, gefitinib or erlotinib are used.

In accordance with the invention, a compound with a protective action for nerve cell can be reselected by adding PPARδ agonist to a culture cell system where toxic substances such as thapsigargin, MPP+ and staurosporine are preliminarily allowed to react and reselecting a compound improving the survival rate. The compound selected by such method can be used as an active ingredient of a therapeutic agent for neurodegenerative diseases such as cerebral infarction and Parkinson's disease. Thus, the invention is very useful for research works for creating novel pharmaceutical agent.

The invention discloses a novel Streptomyces strain and application thereof. The strain is named as streptomyce sp. HS-HY-153, and the preservation number thereof is CGMCC NO. 14806; the invention also discloses a method for preparing Staurosporine by culturing the strain HS-HY-153.

The invention discloses a semisynthetic method of staurosporine derivatives, which comprises the following steps: dissolving raw materials of fermented staurosporine products in a mixed solution of methanol and dichloromethane, adding sodium tungstate dihydrate and an aqueous hydrogen peroxide solution, stirring away from light, adding saturated sodium bisulfite to terminate the reaction, adding hydroxylamine hydrochloride and pyridine, performing extraction, concentration, and recrystallization to obtain a staurosporine derivative 1; dissolving the staurosporine derivative 1 with DMF, adding a TiCl3 aqueous solution, extracting with ethyl acetate for 3 times, washing the organic layer, performing drying by distillation, separation, elution, and crystallization to obtain a staurosporine derivative 2. The invention has cheap and easily available raw materials, and a high yield, and the obtained staurosporine derivatives have important application value in the anti-tumor aspect.

The invention discloses applications of staurosporine compounds in preparing medicines for treating cancer, inflammation or AIDS. The compounds are obtained through separation and purification from actinomycetes, and are identified to be staurosporine compounds. The functional research shows that the compounds have relatively high activity for prostate cancer cells, and also have a relatively highinhibiting effect for Brd4 protein, and therefore, the compounds have good application prospects in preparing the medicines for treating tumor, HIV, leukemia and other diseases.

The present invention relates to a staurosporine preparation method, wherein a molecular formula of the staurosporine is C28H26N4O3, and the staurosporine is prepared through streptomyces scabiei var.xuchangensis CGMCC No.5213 fermentation. According to the present invention, streptomyces scabies fermentation is adopted to produce the staurosporine so as to provide a new way for staurosporine production; and the staurosporine produced from the streptomyces scabiei var.xuchangensis provides strong antagonism for a plurality of plant pathogenic fungi, provides a strong in vitro deactivation effect for TMV, and has development potential as an agricultural antibiotic.

The invention relates to a novel staurosporine analogue and a preparation method and applications thereof, wherein two staurosporine analogue molecules with a novel structure is prepared from the Streptomyces Sp.FMA which is separated from the soil sample of the Sanya Mangrove in Hainan Island of China and has the strain preservation number of CCTCC M 2010021. The in vitro cytotoxicity test proves that the compound has cytotoxicity to leukemia cell HL-60 and lung cancer cell A549 and can be used as the cell antiblastic.

The invention relates to phylum porifera symbiosis streptomycete SP6206, belonging to the field of phylum porifera symbiosis streptomycete fermentation. The preservation number of the phylum poriferasymbiosis streptomycete SP6206 is CCTCCM2017451. The invention also discloses a method for producing staurosporine by fermenting the phylum porifera symbiosis streptomycete SP6206, which comprises thefollowing steps: (1) culturing a seed solution of the SP6206; (2) inoculating the cultured seed solution of the SP6206 to a fermenting culture substrate, and carrying out fermented culture, thereby obtaining a fermentation solution; and (3) separating staurosporine from the fermentation solution. According to the phylum porifera symbiosis streptomycete SP6206, the highest yield of the staurosporine reaches 320mg / L and is greatly increased compared with that of the common wild streptomycete staurosporine in the prior art. The staurosporine can be used for preventing and treating the colletotrichum gloeosporioides of Chinese yams, the minimal inhibitory concentration of the staurosporine for preventing and treating the colletotrichum gloeosporioides of the Chinese yams is 8 microg / ml, and the minimal inhibitory concentration of the staurosporine is 1 / 4 that of the positive drug cycloheximide.

The invention discloses a culture medium which is applicable to culturing staurosporine producing bacteria for producing staurosporine; the culture medium with pH value of 7.0 comprises carbon sources, organic nitrogen sources and inorganic salt, wherein, the inorganic salt comprises calcium salt; the carbon sources are selected from two or more than two of the following three groups of components, namely, A, B and C, wherein, at least two components are selected from different groups, group A: glucose, group B: amidulin, corn starch and potato starch, and group C: oats and maltodextrin; and / or, the organic nitrogen sources are selected from soybean cake powder, yeast extract, yeast cream and kapok meal; and / or, the inorganic salt is also added with magnesium salt. The invention also discloses a method for producing staurosporine from staurosporine producing bacteria by adopting the culture medium. By adopting the fermentation medium for producing staurosporine, the thalli of the staurosporine producing bacteria grows fast, the mycelia are not easy to clot, the yield of fermentation products is high, and the relative potency is optimized 230 percent of a former culture medium.

The invention relates to C12Q contained enzyme or microorganism measurement or inspection field, and particularly relates to a screening method for an enzyme spectrum of kinase of a tumor inhibitor. The screening method includes the following parts and steps: step one, determining and optimizing the kinase concentration; step two, measuring kinase ATP Km; and step three, measuring IC50 of a positive inhibitor staurosporine or other compounds. With adopting of the above steps, the screening method has the advantages that 66 kinds of kinases can be detected at a time, the detection scale is large, the speed is fast, and the sensitivity is high.

The invention relates to a new crystalline form II of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of crystalline form II of N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans. The invention relates to the amorphous forms of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of amorphous N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans.

The invention discloses a culture medium which is applicable to culturing staurosporine producing bacteria for producing staurosporine; the culture medium with pH value of 7.0 comprises carbon sources, organic nitrogen sources and inorganic salt, wherein, the inorganic salt comprises calcium salt; the carbon sources are selected from two or more than two of the following three groups of components, namely, A, B and C, wherein, at least two components are selected from different groups, group A: glucose, group B: amidulin, corn starch and potato starch, and group C: oats and maltodextrin; and / or, the organic nitrogen sources are selected from soybean cake powder, yeast extract, yeast cream and kapok meal; and / or, the inorganic salt is also added with magnesium salt. The invention also discloses a method for producing staurosporine from staurosporine producing bacteria by adopting the culture medium. By adopting the fermentation medium for producing staurosporine, the thalli of the staurosporine producing bacteria grows fast, the mycelia are not easy to clot, the yield of fermentation products is high, and the relative potency is optimized 230 percent of a former culture medium.

The invention discloses a Staurosporine aldehyde substituted derivative as well as a preparation method and application thereof. The compound, namely the Staurosporine aldehyde substituted derivative, has structures represented by a formula I and a formula II. The compound provided by the invention can be used for treating cancers such as acute and chronic leukemia, lymph cancer, breast cancer, lung cancer as well as diseases such as AIDS, coronary heart disease, diabetes mellitus and senile dementia which are relevant with protein kinase inhibition. The preparation method comprises the steps of carrying out fermentation by virtue of a marine actinomycete rice solid culture medium, carrying out extraction by virtue of ethyl acetate, carrying out gel column chromatography and high performance liquid chromatography and separation on the obtained ferment, so as to obtain the Staurosporine aldehyde substituted derivative. The preparation method is easy in operation and implementation.

IL1A or a gene located near IL1A on chromosome 2q14 may contribute to hepatotoxicity, as measured by increased serum levels of aspartate transaminase, during N-benzoyl-staurosporine treatment for macular edema. Accordingly, genetic polymorphisms in the IL1A gene are useful as biomarkers for predicting staurosporine derivative-mediated hepatotoxicity.

The invention discloses a 7-carbonyl staurosporine compound, and a preparation method and an application thereof. The staurosporine compound provided by the invention has a structural formula as shownin a formula (I) which is described in the specification. The staurosporin compound provided by the invention is prepared through the following steps: subjecting actinomycete to fermentation in a rice solid medium, then carrying out extraction and filtration so as to obtain a crude extract, and carrying out separation and purification. The staurosporin compound provided by the invention has significant antitumor activity, specifically has high activity to prostate cancer, colon cancer, pancreatic cancer and gastric cancer, and can be used for preparation of anticancer drugs.

The invention relates to a new crystalline form II of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of crystalline form II of N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans. The invention relates to the amorphous forms of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of amorphous N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans.

The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein. In various embodiments, the present invention contemplates a kit comprising an agent that increases prostaglandin EP receptor signaling and staurosporine.

The invention discloses 3-O-demethylation-4-N-demethylation-4-N-ethanoyl-staurosporine and a preparation method and an application thereof. The compound has the antineoplastic activity and the proteinkinase inhibiting effect, and can be used for preparing pharmaceuticals of protein kinase inhibitors and antineoplastic pharmaceuticals. The compound is prepared and obtained from a fermentation product of actinomycetes (Streptomyces sp. CICC 11026) by using a rice fermentation method. The preparation method comprises the following steps: after executing the ethyl acetate extraction to the fermentation product, separating and purifying by using a gel chromatography and a high performance liquid chromatography, to obtain the compound. The preparation method is easy to operate and carry out.

The invention belongs to the technical field of plant disease control, and particularly relates to application of a kinase inhibitor Staurosporine to improvement of bacterial wilt resistance of plants. According to the invention, an FER gene related to bacterial wilt resistance is excavated, the FER kinase inhibitor is screened in a model plant arabidopsis thaliana, the bacterial wilt resistance adjusting effect of the kinase inhibitor is verified in the arabidopsis thaliana, finally, the function of the related kinase inhibitor is verified in tobacco seriously damaged by bacterial wilt, and it is found that the kinase inhibitor Staurosporine can inhibit the kinase activity of FER, so that the resistance of tobacco to bacterial wilt is improved.

The invention discloses applications of staurosporine in resistance of Coccidiosis in chicken. According to the present invention, staurosporine can be uniformly mixed with an acceptable auxiliary material, and the obtained mixture can be added to a feed so as to effectively resist the reproduction of Coccidiosis in chicken; compared to the conventional anticoccidial drug sulfachloropyrazine sodium soluble powder, the product of the present invention has the significant anticoccidial effect; and with staurosporine, the serious drug resistance problem caused by the use of anticoccidial drugs inthe current breeding industry can be effectively alleviated, the research and development of new drugs on the basis can be accelerated, and the important benefits can be provided for the environmentally friendly and healthy development of breeding industry.

The invention discloses a staurosporine extraction method which comprises the following steps: 1) plate-frame filtration; 2) acetone extraction; 3) extraction; and 4) crystallization and vacuum drying. The staurosporine extraction method disclosed by the invention has advantages of low production cost, short extraction period, simple operation, stable method, easy amplification, and extremely highpractical value in industrial production.

The invention discloses staurosporine derivatives, which can be used for development of anti-tumor related drugs and drugs for protein kinase, tyrosine kinase and other kinase inhibition related diseases. The invention also provides a preparation method of the staurosporine derivatives. The method includes: subjecting actinomycetes to fermentation in a rice solid medium, then performing ethyl acetate extraction to obtain a fermentation crude extract, and employing gel column choromatography, silica gel column chromatography, medium pressure liquid chromatography and high performance liquid chromatography for separation and purification, thus obtaining the product. The method is easy to operate and implement. The staurosporine derivatives provided by the invention have novel structure types, and are firstly discovered in natural products. The staurosporine derivatives are simple in experimental operation, are easy for expanded production, and have good application prospects.

The invention relates to a new crystalline form II of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of crystalline form II of of N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans. The invention relates to the amorphous forms of N-benzoyl-staurosporine; compositions containing the same; processes for the preparation thereof; and the use of amorphous N-benzoyl-staurosporine in diagnostic methods or therapeutic treatment of warm-blooded animals, especially humans.

The invention discloses a staurosporine compound as well as a preparation method and application thereof. The structure of the compound is of formula I shown in the specification. The compound has antitumor activity and BRD4 inhibition activity, can be used for treating cancer diseases such as leukemia, breast cancer and colon cancer related to over cell proliferation or abnormal cell proliferation, and can be also applied to research and development of medicines related to anti-HIV incubation and anti-human papillomatosis viruses (HPV). According to the preparation method, the staurosporine compound is prepared from marine actinomycete via solid fermentation culture, and a fermentation product is extracted with ethyl acetate and is further separated and purified by using gel chromatography and inversed phase chromatography. The preparation method is easy to operate and implement.

Pharmaceutical compositions and methods for treating epithelial cancers and precancerous lesions employ indole carbazole compounds, such as staurosporine. Compositions containing these compounds are administered to a patient in an effective amount and may be administered topically.

The invention provides a method for promoting the accumulation of staurosporine, and specifically discloses a culture medium for promoting the accumulation of staurosporine, which greatly promotes the accumulation of staurosporine by adopting different vitamin combinations and medium formulas. At the same time, by adding carbon source, the fermentation yield can be increased by more than 40%. The technical scheme provided by the invention is simple and feasible, further improves the production efficiency of the staurosporine, reduces production costs, and facilitates the industrial production and application of the staurosporine.

The invention relates to phylum porifera symbiosis streptomycete SP6206, belonging to the field of phylum porifera symbiosis streptomycete fermentation. The preservation number of the phylum poriferasymbiosis streptomycete SP6206 is CCTCCM2017451. The invention also discloses a method for producing staurosporine by fermenting the phylum porifera symbiosis streptomycete SP6206, which comprises thefollowing steps: (1) culturing a seed solution of the SP6206; (2) inoculating the cultured seed solution of the SP6206 to a fermenting culture substrate, and carrying out fermented culture, thereby obtaining a fermentation solution; and (3) separating staurosporine from the fermentation solution. According to the phylum porifera symbiosis streptomycete SP6206, the highest yield of the staurosporine reaches 320mg / L and is greatly increased compared with that of the common wild streptomycete staurosporine in the prior art. The staurosporine can be used for preventing and treating the colletotrichum gloeosporioides of Chinese yams, the minimal inhibitory concentration of the staurosporine for preventing and treating the colletotrichum gloeosporioides of the Chinese yams is 8 microg / ml, and the minimal inhibitory concentration of the staurosporine is 1 / 4 that of the positive drug cycloheximide.