52 results about "SIRT6" patented technology

A method of inducing NAD+ synthesis in a subject. The method comprises administering to the subject a therapeutically effective amount of resveratrol or a functionally equivalent analogue or derivative thereof. NAD+ synthesis increases the activity of Poly(ADP-ribose) polymerase (PARP) enzymes and sirtuin enzymes. The PARP enzyme is PARP-1 or PARP-2 and the sirtuin enzyme is selected from the group consisting of SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7.

The invention relates to the surprising finding that biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1 R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, S0CS2, and DCN are differentially expressed in control samples as compared to samples from patients having endometrial cancer and are therefore useful for detecting endometrial cancer. In particular these biomarkers having excellent sensitivity, specificity, and / or the ability to separate affected from non affected individuals. Furthermore, the inventors found that the differential expression of these biomarkers in primary endometrial cancer tumor tissue is correlated to their expression level in uterine fluid samples as compared to control values.; Thus these biomarkers are robust in that they are found to be differentially expressed in several different types of samples from affected individuals.

The invention discloses an application of a vascular endothelial cell SIRT6 gene, and a drug, and belongs to the field of functions and applications of genes. Endothelial cell-specific SIRT6 knockoutmice are used as experimental subjects, and a result of comparison of the experimental subjects and a control group SIRT6flox / flox mice shows that the vascular endothelial NO release level and the NOSenzyme activity of the endothelial cell-specific SIRT6 knockout mice are significantly reduced, the vasodilation function and the barrier function of the endothelial cell-specific SIRT6 knockout miceare impaired, so the loss of SIRT6 in endothelial cells can lead to severe endothelial dysfunction, thereby leading to other cardiovascular diseases. The SIRT6 gene has a protective effect on the endothelial function, and provides a theoretical basis and a clinical basis for the role of the SIRT6 in the research of new targets and strategies for preventing and treating the cardiovascular diseases.

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing RNA virus-related diseases or conditions, herpes virus related diseases or conditions, Sirtuin 6 (Sirt6)-related diseases or conditions, Pax6 related diseases or conditions, and p53 related diseases or conditions.

The invention discloses a quinoline-4-formamide skeleton derivative and application thereof, belonging to the field of chemical medicines. The invention provides a compound as shown in a formula I or pharmaceutically acceptable salt thereof. The invention also provides a preparation method and application of the compound. Biological experiments show that the compound has a very good excitation effect on SIRT6, shows good same-family selectivity and can obviously improve pathological changes related to SIRT 6at an in-vitro molecular level; and particularly, the compound shows good anti-cancer activity in vivo and in vitro, especially pancreatic cancer activity, provides a new choice for development and application of anti-cancer drugs, and has good application prospects.

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing RNA virus-related diseases or conditions, herpes virus related diseases or conditions, Sirtuin 6 (Sirt6)-related diseases or conditions, Pax6 related diseases or conditions, and p53 related diseases or conditions.

A SIRT6 activating molecule as shown in Tables 1-3 and 9, or a compound according to a pharmacophore as described herein.

The invention discloses an application of a Wnt inhibitor ICG001 in the preparation of medicines for treating hematopoietic aregenerative diseases. The Wnt inhibitor ICG001 can inhibit a CBP mediated Wnt signal path in order to inhibit depletion of too high Wnt signal hematopoietic stem cells, induced by SIRT6 deletion. The invention discloses the application of the Wnt inhibitor ICG001 in the preparation of the medicines for treating hematopoietic aregenerative diseases, and an action mechanism of the ICG001 in promotion of regeneration of SIRT6 knockout hematopoietic stem cells.

The invention discloses an application of a Wnt inhibitor ICG001 in the preparation of medicines for treating hematopoietic aregenerative diseases. The Wnt inhibitor ICG001 can inhibit a CBP mediated Wnt signal path in order to inhibit depletion of too high Wnt signal hematopoietic stem cells, induced by SIRT6 deletion. The invention discloses the application of the Wnt inhibitor ICG001 in the preparation of the medicines for treating hematopoietic aregenerative diseases, and an action mechanism of the ICG001 in promotion of regeneration of SIRT6 knockout hematopoietic stem cells.

The invention belongs to the field of organic synthetic medicine and particularly relates to a substituted 6,8-dimercapto-2-phenyl-4H-chromen-4-one derivative, having the structure that is shown in the description. Embodiments of the substituted 6,8-dimercapto-2-phenyl-4H-chromen-4-one derivative prove that the derivative can activate TyrRS-PARP-1 signal pathway such that activation of PARP-1 viaTyrRS leads to a series of protective genes, including tumor inhibiting gene p53 and longevity genes FOXO3A and SIRT6 to be activated; the derivative has good medicinal potential in age defying and DNA restoration drugs, and a new potential option is provided for clinical medication; in addition, a preparation method of a new compound herein is simple, the preparation method has mild reaction conditions, is convenient to perform and control, has low energy consumption, high yield and low cost, and is suitable for industrial production, and the compound produced has high bioactivity, high activity and selectivity, significant drug-likeness, and promising market prospect.

A SIRT6 activating molecule as shown in Tables 1-3 or a compound according to a pharmacophore as described herein.

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing RNA virus-related diseases or conditions, herpes virus related diseases or conditions, Sirtuin 6 (Sirt6)-related diseases or conditions, Pax6 related diseases or conditions, and p53 related diseases or conditions.

The present invention relates to methods of treating pleasant sensation loss in a human subject by administering a SIRT6 activator. The invention also provides methods of treating a pleasant sensation loss in a human female subject by administering a SIRT6 activator, wherein the female subject can be recognized by, for example, the presence of two X chromosomes or circulating a female hormone.

The invention relates to an application of Sirt6 in regulating cell autophagy. The invention further relates to application of the Sirt6 in preparation of a medicament for treating atherosclerosis caused by diabetes. The invention also relates to a medicament for treating atherosclerosis caused by diabetes. The medicament comprises an expression vector with a Sirt6 gene overexpression cassette. According to the application, the influence of the Sirt6 on the deacetylation of the Caveolin-1 protein in the vascular endothelial cells is found for the first time, and the condition that the deacetylation level of the Caveolin-1 protein in the vascular endothelial cells can be changed by adjusting the expression quantity of the Sirt6, so that the autophagy effect and the atherosclerosis process in the cells are influenced is found. Therefore, the invention has important significance and enlightenment for treating atherosclerosis caused by diabetes.

The invention provides compounds having an effect of activating SIRT6 deacetylation activity, or a pharmaceutically acceptable salt of the compounds. The compounds have a structure represented a formula (I) shown in the description. The invention also provides a SIRT6 activator obtained by using the compounds and an application of the SIRT6 activator in preparation of a medicine for treating SIRT6-mediated related diseases.

The invention relates to a nano drug-loaded complex with a targeted myocardial function as well as a preparation method and application of the nano drug-loaded complex. The preparation method comprises the following steps: constructing a novel, safe and efficient nano drug-loaded complex by utilizing a nano material assembly technology, namely preparing phospholipid micelles by taking distearoyl phosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG) as a main raw material, loading fluorescent coumarin 6 (C6), adding ischemia targeting polypeptide CSTSMLKAC (PEP) to be coupled on the outer side of the DSPE-PEG, wrapping an SIRT6 agonist MDL-800 in the DSPE-PEG, and preparing the novel, safe and efficient nano drug-loaded complex. The preparation method comprises the following steps: designing and constructing to obtain a DSPE-PEG-C6-PEP-MDL-800 (DPCP-MDL-800) complex; on the basis, characterization release and in-vivo distribution of the complex and an improvement effect of the complex on myocardial ischemia reperfusion injury of an aged mouse are evaluated. The novel nano drug-loaded complex drug with the ischemic myocardial targeting function provided by the invention is expected to provide a potential solution for myocardial ischemia reperfusion injury of aged mice.

The invention discloses a SIRT6 small molecule agonist and an application thereof. The agonist is a tricyclic bissulfonamide derivative represented by formula (1) or a pharmacologically acceptable salt thereof, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 The same or different, represents hydrogen atom, halogen, said halogen refers to fluorine, chlorine, bromine and iodine, hydroxyl, nitro, amino, carboxyl, acid ester, sulfonamide, mercapto, methoxy, ethoxy, benzyloxy base, methyl, tert-butyl, cyano; R 11 Represents a hydrogen atom, chlorine, nitro, amino, benzyl alcohol, benzyl chloride, benzylamine, carboxyl, and acid ester. The three rings are connected by amide bonds. The invention designs and synthesizes a high-efficiency and low-toxicity SIRT6 small molecule agonist, which can obviously stimulate the activity of SIRT6 in an in vitro experiment, and is of great significance to the development of drugs for related diseases.

The present disclosure provides compounds according to Formula I and pharmaceutically acceptable salts thereof, as well as compositions including such compounds and a pharmaceutically acceptable carrier or excipient. Further provided are methods of inactivating SIRT6 with compounds of Formula I as well as compounds of Formula III, W2—R2—Y—R3, as described herein. In addition, the present technology provides methods of treatment using such compounds to lower LDL levels, lower triglyceride levels, and / or increase glucose tolerance in a subject, and / or to inhibit proliferation of ovarian, colorectal, hepatocellular, non-small cell lung, glioblastoma, osteosarcoma, pancreatic, and skin cancer cells, and / or inhibit liver and / or kidney fibrosis, and / or promote corneal epithelial wound healing.

This invention relates to a method of treating a joint and / or bone disease, slowing progression of a reduction in bone mass, increasing osteoblast formation, decreasing osteoclast formation, and / or reducing osteocyte death, slowing progression of a reduction in joint mobility and / or function, slowing progression of a reduction in cartilage, and / or reducing chondrocyte senescence and / or death by administering a therapeutically effective amount of a SIRT6 activator, optionally with nicotinamide adenine dinucleotide (NAD+) and / or an NAD+ precursor.

The present invention is directed to methods for the use of 5′-adenosine diphosphate ribose (ADPR), and compositions thereof, for treating, managing, or preventing RNA virus-related diseases or conditions, herpes virus related diseases or conditions, Sirtuin 6 (Sirt6)-related diseases or conditions, Pax6 related diseases or conditions, and p53 related diseases or conditions.

The present invention relates to a method for improving glucose homeostasis and / or lowering plasma glucose levels by administering a SIRT6 activator. The present invention also provides a method for treating hyperglycemia, prediabetes, and diabetes, including type I diabetes, type II diabetes, or gestational diabetes, by administering a SIRT6 activator.

The present invention relates to methods of treating depression in human females by administering a SIRT6 activator.

A class of compounds represented by formula (I) or a stereoisomer, a tautomer, a solvate, or a pharmaceutically acceptable salt thereof.

The present invention belongs to the technical fields of biomedicine and molecular biology, and particularly relates to the application of Sirt6 in constructing an animal tumor-bearing model with a normal immune system and tumor immunotherapy. By increasing the activity and expression of Sirt6, the present invention enables human tumor cells to grow into human tumor tissues in mice with a normal immune system. Since the used mice have a perfect immune system, the human cancer cell tumor-bearing model and research results are closer to the actual situation of tumor clinical practice. Therefore, using this research model can be better used for the study of tumor pathogenesis, tumor immunity exploration, and tumor drugs. In addition, activating this gene allows tumor cells in immune-normal mice to escape immune surveillance and grow, indicating that this gene locus is a key point for immune escape during tumor, especially early tumorigenesis. Reverse inhibition of the activity of this gene should be beneficial to tumor prevention and treatment, thus having good practical application value.

The invention discloses an overexpression SIRT6 recombinant lentiviral plasmid vector and a construction method of a cell model of the overexpression SIRT6 recombinant lentiviral plasmid vector. The nucleotide sequence of a gene SIRT6 protein coding region of an SIRT6 DNA double-chain fragment in the recombinant lentiviral plasmid vector is as shown in SEQ ID NO: 1; by utilizing the recombinant lentiviral vector, stable and continuous high expression of SIRT6 is realized, autophagy of endothelial cells is remarkably promoted, apoptosis is inhibited, and the functions of the endothelial cells are maintained, so that a new hope is brought for clinically intervening the functions of the endothelial cells so as to improve cardiovascular diseases; a potential molecular mechanism between SIRT6 and endothelial apoptosis and autophagy can be further researched subsequently, and a useful clue is provided for treating cardiovascular diseases caused by endothelial dysfunction; the important application value is realized.

The present invention belongs to the field of biomedical technology and discloses a method for screening drugs targeting histone deacetylase SIRT6 regulators. Based on testing the affinity between SIRT6 protein and small molecules with SYPRO Orange Protein Gel Staining Solution, this method constructs a drug screening model to screen for SIRT6 regulator-targeting drugs. The drug screening model constructed by the present invention is applicable to screening monomeric compound drugs with strong affinity effects (including agonists and inhibitors) on histone deacetylase SIRT6, and the action sites of the screened compounds are clear; the screening of monomeric compound drugs using this drug screening model has the advantages of high throughput, small protein consumption, low concentration, low cost, strong specificity, and convenient operation, providing a new and effective option for the screening of histone deacetylase SIRT6 regulators in this field, having good application prospects, and successfully screening out monomeric compound drugs with strong targeting effects on SIRT6 protein.

The present invention relates to methods of treating neurodegenerative disease in human subjects by administering an activator of sirtuin 6 (SIRT6) and a nicotinamide adenine dinucleotide (NAD)+ precursor. Exemplary neurodegenerative diseases include, but are not limited to, those where the subject has decreased levels and / or activity of SIRT6, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

The invention discloses an application of lychee seed saponin in preparation of a medicine for treating fatty liver, and belongs to the technical field of medicines. The invention specifically discloses an application of a lychee seed monomer Artungcoside I in preparation of the medicine for treating non-alcoholic fatty liver disease. According to the application of the lychee seed saponin in preparation of the medicine for treating the fatty liver, experiments verify that the lychee seed monomer Artungcoside I is used as an activating agent to activate an SIRT6-Nrf2 pathway, so that the effect of treating non-alcoholic fatty liver is realized, a direction and a basis are provided for clinically developing a new medicine for treating the non-alcoholic fatty liver disease, and a data support is provided for treating the non-alcoholic fatty liver disease.

The application provides application of a SIRT6 activator as an active ingredient in preparation of a medicament for treating and preventing a blood vessel aging related disease. Application of the SIRT6 activator in a blood vessel smooth muscle cell can significantly inhibit aging of the blood vessel smooth muscle cell and increase of an aging related inflammatory factor. In a mouse thoracic aortic aneurysm model constructed by a CaCl2 incubation method, application of the SIRT6 activator can obviously inhibit an aneurysm phenotype.

Provided is a compound. The compound is a compound represented by formula (I) or a stereoisomer, tautomer, solvate, or pharmaceutically acceptable salt thereof.