8 results about "Sphingosine kinase" patented technology

The invention provides an indole compound as well as a preparation method and application thereof. The structural formula of the compound is shown as a formula (I), a formula (II) or a formula (III). The compound provided by the invention is used as an ATP (adenosine triphosphate) competitive sphingosine kinase 1 (SphK1) or 2 (SphK2) inhibitor, and shows strong enzyme inhibition activity and an effect of resisting tumor cell proliferation. Experiments prove that the indole compound provided by the invention has the potential to be developed into an anti-tumor therapeutic drug and an anti-pulmonary arterial hypertension therapeutic drug, and a new direction is provided for the field of anti-cancer therapeutic drugs. The preparation method of the compound is simple, low in cost, free of dangerous reagents and suitable for industrial production.

The disclosure is directed to ABC294640, as free base or as salts thereof, in preparing medicines for treating coronavirus infection or preventing diseases caused by coronavirus infection, and a medicine for preventing coronavirus infection or preventing diseases caused by coronavirus infection.

The invention provides a lotus leaf extract, a preparation method thereof and application of the lotus leaf extract as an active ingredient of a sphingosine kinase 1 agonist, the lotus leaf extract is obtained by mixing, fermenting and culturing lotus leaf powder and bacterial strain fermentation liquor of bacillus subtilis, and the lotus leaf extract is enriched with nuciferine with higher content. The nano vesicles which are uniformly distributed and have the average diameter of 90 to 180nm are reserved; the lotus leaf extract can be used as an SPHK1 agonist, and an autophagy-lysosome pathway is activated by activating an SPHK1 pathway, so that abnormal accumulation of cell lipid is effectively inhibited, and a new thought is provided for research and development of skin oil control products.

The invention discloses siRNA of a targeted SPHK1 super enhancer and application of the siRNA in treatment of triple negative breast cancer. The invention reveals that abnormal expression of sphingosine kinase SPHK1 is driven by a specific super enhancer for the first time, SPHK1-SE-targeted double-stranded small interfering RNA (siRNA-SE) is designed by positioning an SE core regulation region on the upstream of an SPHK1 gene, a non-coding regulation element is specifically silenced, and the expression level of SPHK1 mRNA and protein is remarkably reduced. Further research finds that siRNA-SE can effectively reverse up-regulation of SPHK1 expression in TNBC cells induced by Niraparib, the killing effect of Niraparib on tumor cells is enhanced, the synergistic anti-tumor effect is achieved, the treatment sensitivity of Niraparib in the TNBC cells is remarkably improved, and a treatment means based on SE precise intervention is provided for TNBC.

The application provides a 4-substituted phenylacetamide compound and a preparation method and application thereof, and a structural formula of the compound is shown as formula (I) or (II). The compound provided by the application is a kind of sphingosine kinase 2 (SphK2) targeted small molecule, can effectively inhibit SphK2 enzyme activity and human hepatoma (HepG2), murine hepatoma (Hepa1-6), human colon cancer (HCT116), murine colon cancer (MC-38), cervical cancer (MCF-7), gastric cancer (HGC-27) and other cancer cell proliferation and migration, and the inhibiting effect is better than that of a known inhibitor ABC294640, has the potential to be developed into a new anticancer drug. The synthesis steps of the compound are simple, the requirement for equipment is low, and the operation is simple, so that the yield of the reaction can be greatly improved, and the production cost is further saved.

The invention provides a 4-substituted phenylacetamide compound as well as a preparation method and application thereof. The structural formula of the compound is shown as a formula (I) or (II). The compound provided by the invention is a sphingosine kinase 2 (SphK2) targeting micromolecule, can effectively inhibit SphK2 enzyme activity and proliferation and migration of cancer cells such as human liver cancer (HepG2), mouse liver cancer (Hepa1-6), human colon cancer (HCT116), mouse colon cancer (MC-38), cervical cancer (MCF-7), gastric cancer (HGC-27) and the like, and has a better inhibition effect than that of a known inhibitor ABC294640; the polypeptide has the potential of being developed into a novel anti-cancer treatment drug. The synthesis steps of the compound are simple, the requirement on equipment is low, the operation is simple, the reaction yield can be greatly improved, and the production cost is further saved.

The present invention provides a recombinant genetically engineered bacterium for producing phytosphingosine, and its preparation method and use, belonging to the field of genetic recombination fermentation technology. The recombinant genetically engineered bacterium of the present invention is obtained by overexpressing the serine palmitoyltransferase LCB1 gene, LCB2 gene, tsc3 gene, 3-dehydrodihydrosphingosine reductase tsc10 gene, sphingosine hydroxylase sur2 gene, serine integrin tms1 gene, phosphoglycerate dehydrogenase ser3 gene in the genome of Saccharomyces cerevisiae, and knocking out the sphingosine kinase phospho-LCB4 gene, ceramide synthase LAG1 gene and LAC1 gene, LDB16 gene, sphingolipid homeostasis protein orm1 gene and orm2 gene, L-serine deaminase CHA1 gene, L-serine hydroxymethyltransferase SHM1 gene and SHM2 gene, and fatty acid elongase elo2 gene. The method for producing phytosphingosine using the recombinant genetically engineered bacterium is cost-effective, simple and efficient, with high phytosphingosine yield, and suitable for practical promotion and application.

The present disclosure relates to compositions and methods useful for the treatment and / or prevention of obesity and obesity-related diseases in a subject in need thereof. In various embodiments, the present disclosure relates to uses of compounds that are inhibitors of sphingosine kinase-2 (SphK2), dihydroceramide desaturase (DES1) and / or hexosylceramide synthase (GCS), such as opaganib, in the treatment and / or prevention of obesity and obesity- related diseases.