37 results about "Sphingosine kinase" patented technology

The invention relates to compounds, pharmaceutical compositions thereof, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease,

The invention includes processes mainly for the treatment of a inflammatory diseases, such as inflammatory bowel disease, arthritis, atherosclerosis, asthma, allergy, inflammatory kidney disease, circulatory shock, multiple sclerosis, chronic obstructive pulmonary disease, skin inflammation, periodontal disease, psoriasis and T cell-mediated diseases of immunity, including allergic encephalomyelitis, allergic neuritis, transplant allograft rejection, graft versus host disease, myocarditis, thyroiditis, nephritis, systemic lupus erthematosus, and insulin-dependent diabetes mellitus. The processes involve treating a patient with a pharmaceutical composition containing an active ingredient that inhibits the activity of sphingosine kinase.

The invention relates to substituted adamantane compounds, pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

The invention relates to substituted adamantane compounds, pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

The invention includes processes mainly for the treatment of angiogenic diseases, such as diabetic retinopathy, arthritis, cancer, psoriasis, Kaposi's sarcoma, hemangiomas, myocardial angiogenesis, atherosclerosis, and ocular angiogenic diseases such as choroidal neovascularization, retinopathy of prematurity (retrolental fibroplasias), macular degeneration, corneal graft rejection, rubeosis, neuroscular glacoma and Oster Webber syndrome. The processes involve treating a patient with a pharmaceutical composition containing an active ingredient that inhibits the activity of sphingosine kinase.

Disclosed is a non-natural ceramide compound effective for a sphingosine kinase activator, and thus useful for a skin disease treating agent. The sphingosine kinase activator enhances production of sphingosine-1-phosphate to show various physiological activities provided by sphingosine-1-phosphate. The physiological activities include the effects of: controlling multiplication and differentiation of keratinocytes, multiplication of fibroblasts and collagen synthesis, resulting in treatment of wounds, recovery of damaged skin functions in atopic dermatitis and psoriasis; inhibiting wrinkles and skin irritation caused by ultraviolet rays, followed by improvement of wrinkles and inhibition of skin aging; and reducing skin atrophy, which is a typical side effect of local application steroids. Therefore, the sphingosine kinase activator is useful for a skin disease treating agent for treating skin wounds, wrinkles, atopic dermatitis, eczema, psoriasis, or skin atrophy caused by side effects of local application steroids.

Amidine analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 & SphK2) are provided. The compounds can prevent angiogenesis in tumor cells.

Disclosed herein are novel human nucleic acid sequences that encode polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

The present invention relates generally to a method of modulating smooth muscle cell functioning and agents useful for same. More particularly, the present invention relates to a method of modulating smooth muscle tone by modulating intracellular sphingosine kinase mediated signalling. The method of the present invention is useful, inter alia, in the treatment and / or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate smooth muscle tone, in particular aberrant, unwanted or otherwise inappropriate vascular, bronchial or intestinal smooth muscle tone.

The invention belongs to the technical field of biomedicine and particularly relates to sphingosine kinase 1 and its fusion protein and application, namely sphingosine kinase 1 and application of an active amino acid sequence having its activity in the preparation of protein drugs to prevent and / or treat obesity, hyperlipemia or diabetes mellitus. The invention also provides a protein drug comprising sphingosine kinase 1 or an ammino acid sequence having its activity. The invention also provides application of the protein drug, an encoding gene, an expression construction and a host cell in the preparation of drugs to prevent and / or treat obesity, hyperlipemia or diabetes mellitus. It is discovered herein that sphingosine kinase 1 and its fusion protein have significant glucose-lowering and weight-reducing effects and are applicable to the preparation of protein drugs to control obesity and other metabolic diseases as well as diabetes mellitus.

The invention provides application of a sphingosine kinase inhibitor to preparation of a medicine for treating hepatic fibrosis. The sphingosine kinase inhibitor is an SphK1 inhibitor 5C or an SphK2 inhibitor ABC294640 or SphK inhibitors SK I to II. The medicine prepared from the SphK inhibitor is used for blocking inflammatory reaction and collagen deposition, which promote the hepatic fibrosis,so that the activation of hepatic stellate cells is inhibited and a pathological process of the hepatic fibrosis is alleviated, and furthermore, the development of the hepatic fibrosis is radically prevented. The invention provides a novel medicine source for the medicine for treating the hepatic fibrosis. The technology provided by the invention is financially aided through Key Project of NaturalScience Foundation of China (81530102), Key Project of Natural Science Foundation of Guangdong (2016A030311014) and Guangdong Technology Plan (2017A020211007).

Amidine analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 & SphK2) are provided. The compounds can prevent angiogenesis in tumor cells.

Provided are novel compositions which uniquely inhibit sphingosine kinase Type 1 (SphK1) and which are useful in a number of applications including killing or damaging cancer cells, inducing apoptosis, inhibiting growth, metastasis and development of chemoresistance in cancer cells, leukemia, increasing the effectiveness of anti-cancer agents, attenuating immune reactivity, inhibiting survival signaling in cancer cells, and reducing symptoms of multiple sclerosis.

The present invention relates generally to a method of modulating hyperglycaemia-induced endothelial cell functioning and agents useful for same. More particularly, the present invention relates to a method of modulating hyperglycaemia-induced vascular endothelial cell functioning by modulating intracellular sphingosine kinase-mediated signalling. The method of the present invention is useful, inter alia, in the treatment and / or prophylaxis of the adverse vascular endothelial cell functioning associated with conditions characterised by hyperglycaemia, and / or diabetes mellitus, per se.

The invention relates to compositions and methods for inhibiting sphingosine kinase and for treating hyperproliferative disease.

The present invention relates to compounds of the formula (I), where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, M1, M2, M3, M4, Y1, Y2, V, W, n, m and o have the meaning specified in claim 1, and to physiologically compatible salts, derivatives, prodrugs, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios, for use in the treatment of diseases that are influenced by inhibiting sphingosine kinase 1.

The invention relates to an application of a sphingosine kinase 1 inhibitor in preparation of a medicine for preventing and / or treating a secondary brain injury after cerebral hemorrhage, and belongsto the technical field of medical technologies. The invention provides the application of the sphingosine kinase 1 inhibitor in the preparation of the medicine for preventing and / or treating the secondary brain injury after cerebral hemorrhage. An existing sphingosine kinase 1 inhibitor 5C is applied to the preparation of the medicine for preventing and / or treating the secondary brain injury aftercerebral hemorrhage. A new source is provided for the preparation of the medicine for preventing and / or treating the secondary brain injury after cerebral hemorrhage, and meanwhile, a new medicinal value of the sphingosine kinase 1 inhibitor 5C is explored. The technology is funded by Guangxi Science and Technology Base and Talent Special Fund (Guike AD18281013) and Guangxi Natural Science Foundation General Program (2020GXNSFAA259036) Guangxi Natural Science Foundation of Youth Fund (2018GXNSFBA138046). The structural formula of the sphingosine kinase 1 inhibitor is shown in the specification.

The invention relates to inhibitors of Sphingosine Kinase enzymatic activity, and methods of treating diseases and disorders by administering inhibitors of Sphingosine Kinase enzymatic activity.

The invention relates to prodrugs of hydroxyl-substituted adamantane compounds, pharmaceutical compositions thereof, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

The invention discloses a double-gene modified stem cell as well as a preparation method and application thereof, and further provides a pharmaceutical composition containing the stem cell. The stem cell comprises a first exogenous nucleic acid and a second exogenous nucleic acid which are located in the same expression vector. The first exogenous nucleic acid encodes a nucleotide sequence comprising a first protein, and the first protein is selected from adiponectin, an adiponectin variant or a first fusion protein comprising the adiponectin or the adiponectin variant. The second exogenous nucleic acid encodes a nucleotide sequence comprising a second protein, and the second protein is selected from sphingosine kinase I, a sphingosine kinase I variant, or a second fusion protein comprising the sphingosine kinase I or the sphingosine kinase I variant. The stem cell modified by double genes provided by the invention shows a synergistic effect of an Adiponectin gene and a mutated SPHKI gene, and can obviously reduce the blood sugar and blood fat of a tested animal and reduce the weight.

A composition and a kit for treating cancer comprising N,N-dimethylphytosphingosine. The composition represses the activity of sphingosine kinase, and therefore, intercepts various mechanisms which sphingosine kinase induces. For example, the composition blocks the phosphorylation of ceramide and sphingosine, thereby maintaining high concentration of ceramide and sphingosine. The ceramide and sphingosine induce apoptosis in cancer cells. Therefore, the composition according to the present invention induces apoptosis in cancer cells and accordingly kills the cancer cells.

The present invention relates generally to a method of modulating endothelial cell functional characteristics and to agents useful for same. More particularly, the present invention relates to a method of modulating vascular endothelial cell pro-inflammatory and angiogenic phenotypes by modulating the functional levels of intracellular sphingosine kinase. The method of the present invention is useful, inter alia, in relation to the treatment and / or prophylaxis of conditions which are characterised by inadequate endothelial cell functioning and may include conditions such as vascular engraftment, organ transplantation or wound healing or conditions which are characterised by an aberrant endothelial cell inflammatory or angiogenic phenotype. Further, the method of the present invention facilitates the development of agents, such as functionally manipulated endothelial cell populations, for a range of therapeutic and / or prophylactic uses.

Disclosed is the use of (+)-2-borneol in the preparation of a drug for promoting the upregulation of the expression of sphingosine kinase-1 and / or BDNF (a brain-derived neurotrophic factor). Herein, (+)-2-borneol can be used to prepare a drug for promoting the upregulation of the expression of the sphingosine kinase-1 and / or the brain-derived neurotrophic factor. The drug can induce astrocyte spreading and migration, oligodendrocyte differentiation and survival, and neurite growth and nerve regeneration, and can promote the upregulation of the expression of the brain-derived neurotrophic factor, promote the survival of neurons and the growth of axons, inhibit the expansion of the infarct volume, and achieve the effect of repairing damage at the site of an immediate injury while preventing further expansion of the infarct area to completely treat brain damage, so that the long-term therapeutic effect thereof is significantly improved.

The present invention relates generally to a method of modulating the growth of cells and, more particularly, to a method of down-regulating the growth of neoplastic cells. The present invention is useful, interalia, in the therapeutic and / or prophylactic treatment of cancers such as, but not limited to, solid cancers such as cancers of the colon, stomach, lung, brain, bone, oesophagus, pancreas, breast, ovary or uterus.

The present invention provides a sphingosine kinase 1, a fusion protein comprising the same, and a use thereof. The sphingosine kinase 1 and the fusion protein comprising the same have significant effects in lowering blood sugar and body weight, and are useful for the preparations of protein drugs for controlling metabolic diseases such as obesity and diabetes. It also provides a protein drug, which is a fusion protein containing a sphingosine kinase 1 or an amino acid sequence having the activity thereof. The fusion protein comprises a sphingosine kinase 1 (SPHK1) or an amino acid sequence having the activity thereof, a FC sequence and a linker sequence. The protein drug can significantly decrease blood sugar, blood fat and body weight, and improve fat metabolism.

The invention relates to prodrugs of hydroxyl-substituted adamantane compounds, pharmaceutical compositions thereof, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

The invention relates to compounds of formula (I), wherein R1, R2, R3, R4, R5, R6, R9, R10, R11, Q and W are as defined in claim 1 and precursors thereof are inhibitors of spingosine kinase and can be used, for instance, for the treatment of tumors.