45 results about "Transcription inhibitor" patented technology

This invention relates to a peptide or protein capable of converting a transcription factor into a transcriptional repressor, a gene encoding such peptide or protein, a chimeric protein in which the aforementioned peptide or protein is fused to a transcription factor, a chimeric gene in which the gene encoding a peptide or protein is fused to a gene encoding a transcription factor, a recombinant vector having such chimeric gene, and a transformant comprising such recombinant vector. The peptide of the invention that is capable of converting a transcription factor into a transcriptional repressor is very short. Thus, it can be very easily synthesized, and it can effectively and selectively repress the transcription of a specific gene. Accordingly, such gene is applicable to and useful in a wide variety of fields, such as repression of the expression of cancerous genes and regulation of the expression of genes encoding pigment-metabolic enzymes.

The present invention provides methods and compositions for regulating gene expression using transcription factors linked to proteins that localize to the transcriptional machinery.

The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and γ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.

The invention discloses ingenol and application of a derivative of ingenol in enhancement of generation of lysosome. The application specifically comprises optional application of HEP14 or the derivative thereof in the following applications: induction of generation of the lysosome; preparation of drugs for induction of generation of the lysosome; and preparation of drugs for treating and / or preventing lysosome functional disturbance related diseases. HEP14 can activate PKC alpha and PKC delta, on one hand, transcription factors TFEB are activated through two parallel signal pathways, and on the other hand, transcription inhibitors are inactivated and are finally used as 'molecular switches' to control generation of the lysosome. Activation of PKC causes inactivation of GSK3 beta, then transfer of TFEB dephosphorylation to cell nucleus is caused, meanwhile, PKC which is in an activated state can further activate MAPK kinase JNK2 and p38 and phosphorylate ZKSCAN3, and ZKSCAN3 can be transferred to cytoplasm from cell nucleus. HEP14 does not affect activity of mTORC1, therefore, cell metabolism balance is not disturbed, and the ingenol is a perfect drug for treating lysosome related diseases possibly.

The invention discloses a potato tuber anthocyanin synthesis transcription inhibitor StMYB44-1 and application thereof, wherein a gene sequence of the StMYB44-1 is shown as SEQ ID NO.1. A preparationmethod of the potato tuber anthocyanin synthesis transcription inhibitor StMYB44-1 comprises the following steps of: selecting plant materials; selecting reagents; extracting RNA and qPCR; constructing an expression vector; and cloning the StMYB44-1 gene sequence according to a designed primer of a potato database, and obtaining a complete coding sequence of the StMYB44-1 from potato meat of a black beauty potato by using cDNA as a template through PCR amplification. The invention discloses the transcription factor StMYB44-1 for inhibiting the potato tuber anthocyanin synthesis at high temperature; and the potato tuber anthocyanin synthesis transcription inhibitor StMYB44-1 has important significance for clarifying a regulation and control mechanism of the potato tuber anthocyanin under the influence of temperature and improving the content of the potato anthocyanin on the basis of the regulation and control mechanism.

The invention relates to discovery of a transcription factor family gene specific to angiosperms, detection on transcription inhibition activity of an encoding protein, and application of the transcription factor family gene in improving plant stress resistance. An experiment on AITRs (ABA-induced transcription repressors) gene knocked-out arabidopsis mutant is utilized to verify enhanced resistance of the mutant to ABA and an abiotic stress. AITRs are further discovered to be widely present in the angiosperms. Based on experiments taking tomatoes and soybeans as examples, expression of AITRs gene of the tomatoes is induced by the ABA, and a protoplast transfection experiment proves that the AITRs of both the tomatoes and the soybeans are transcription inhibitors, which indicates that the AITRs are a novel transcription factor family conserved in the angiosperms, and knocking out corresponding AITRs gene of a plant can enhance resistance of the plant to the abiotic stress. Therefore, the invention provides a transcription factor gene family which can be applied to genetic modification to enhance resistance of the plant to adverse environment.

The invention discloses a GntR family transcription inhibitor mutant, a mutant gene and an application of the mutant gene to preparation of vitamin B2. The amino acid sequence of the mutant has the following mutation relative to the sequence shown in SEQ ID No.3: the 89th amino acid is replaced with M. The 89th amino acid encoding nucleotide in the GntR family transcription inhibitor gene on the chromosome of bacillus subtilis is subjected to site-specific mutagenesis to encode the amino acid M. The vitamin B2 production capacity of the obtained genetically engineered bacterium is greatly improved, and growth of the bacterium is facilitated, so that high application and popularization values are achieved.

The invention discloses a conditionally replicating adenovirus vector for virus replication regulated by a TetR-KRAB-mediated transcription inhibition type Tet-On system, adenovirus E1 region comprises the following components in the following connection sequence: 5'-CMV promoter, TetR-KRAB gene, promoter TRE3G-E1b Pro containing a tetracycline responsive element, EcoR I enzyme cutting site, E1B Delta 55KD protein-deleted adenovirus E1A-E1B19KD gene sequence, enzyme cutting site Spe I and mRNA transcription termination signal SV40polyA-3'; the CMV promoter expresses transcription inhibitor TetR-KRAB; a gene sequence inserted into the two enzyme cutting sites of the EcoR I and the Spe I is a gene fragment from adenovirus E1A translation initiation site to adenovirus E1B19KD protein termination codon, the promoter TRE3G-E1b Pro containing the tetracycline responsive element expresses adenovirus E1A gene, adenovirus E1B19KD gene is expressed by the own promoter of the adenovirus E1B19KD, and the packed adenovirus is named as Ad5-CMV-TetR-KRAB-TRE3G-E1bPro-Delta 55KD. Tests show that the virus can be loaded into mesenchymal stem cells for application in study of tumor therapy.

The invention belongs to the technical field of plant genetic engineering, and particularly relates to a function and application of a transcription inhibitor LIP1 for regulating and controlling rice yield. A cloned LIP1 protein gene interacts with a LAX1 gene, and is expressed in the later developing stage of the meristem of a lateral spikelet and inhibits the transcriptional activity of the LAX1 protein by interaction with the LAX1. The deletion or space-time ectopic expression of the LIP1 gene functions can change the space-time activity of the LAX1 protein and influence formation of rice spikelet. The spatio-temporal expression of the LIP1 defines the activation range of LAX1 in spikelet lateral meristem, and ensures formation of rice lateral spikelet so as to control the yield. By utilizing the cloned LIP1 gene and the encoding protein thereof, the space-time activity of LAX1 can be changed by regulating and controlling the expression activity of the LIP1 gene through a gene manipulation means, so that the formation of spikelet is regulated and controlled, and important significance is achieved on genetic improvement of rice yield traits.

Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1′-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (P4N, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxypehnyl])butane tetrakishydrochloride salt) has an IC50 of 0.88 μM.

The invention relates to an engineering bacterium over-expressing carbon catabolite repression effect transcription inhibitor gene and a construction method thereof. The over-expressed carbon catabolite repression effect transcription inhibitor gene ccpN is obtained by cloning polysaccharide flocculant by using PCR amplification in a synthesis pathway, the nucleotide sequence is as shown in SEQ IDNo.1. The carbon catabolite repression effect transcription inhibitor gene ccpN is cloned by using PCR amplification, the gene ccpN fragment are ligated into an expression vector, and introduced intoBacillus licheniformis, and the engineering bacterium of the target gene is obtained by tetracycline resistance screening. The construction method is as follows: designing PCR primers; inserting thetarget gene into downstream multiple cloning sites of PHY300PLK-PamyL-TTamyL constitutive promoter PamyL so as to obtain expression plasmids, and introducing the plasmids into escherichia coli DH5alpha for amplification; and transferring the over-expressed plasmids by electric shock into the Bacillus licheniformis, selecting transformants, and performing verification to obtain recombinant bacteriaof Bacillus licheniformis.

The invention discloses application of sulforaphane and derivatives thereof as a bacterial effector protein transcription inhibitor. The invention provides an application of sulforaphane and derivatives thereof in any one of application of the following 1) and 7): 1) prevention and treatment of pathogenic bacteria; 2) improvement of the resistance of plants to pathogenic bacteria; 3) inhibiting ofpathogenicity of pathogenic bacteria; 4) inhibiting of the function of a pathogenic bacterium III type secretion system; 5) inhibiting of the expression of effector protein related genes of a pathogenic bacterium type III secretion system; 6) inhibiting of the expression of a pathogenic bacteria transcription factor hrpL; and 7) using as a pathogenic bacteria effector protein transcription inhibitor. Experiments prove that the sulforaphane and the derivatives thereof can inhibit the function of a pathogenic bacteria type III secretion system by specifically inhibiting transcription of the pathogenic bacteria type III secretion system, can resist invasion of pathogenic bacteria without destroying interaction between plants and beneficial microorganisms, and have a wide application prospectin prevention and treatment of plant pathogenic bacteria.

The invention discloses an application of rose acid A in anti-senescence of hematopoietic stem cells. Hematopoietic stem cells undergo complex processes such as self-renewal, differentiation, aging and death to maintain the production of lifelong hematopoietic cells. Although the basic components of hematopoietic system are maintained during aging, the function and quantity of hematopoietic stem cells decrease gradually, which leads to the decrease of hematopoietic function and the decline of immune function. Epoxycarotenal A, Epoxycarotenal B, Rosin A or Rosin D can resist senescence of hematopoietic stem cells by inhibiting transcription of p16 gene. Epoxycarotenal A, Epoxycarotenal B, Rosin A or Rosin D can be made into p16 gene transcription inhibitor and anti-senescence drug of hematopoietic stem cells.

This disclosure provides methods of using BAF complex modulating compounds as inhibitors of BAF-mediated transcription in target cells. The BAF complex modulating compounds include 12-membered macrolactam compounds that can target a BAF-specific subunit (e.g., ARID1A) to prevent nucleosomal positioning, relieving transcriptional repression of HIV-1. The subject methods can provide for reversal of latency of HIV-1 in cells in vitro or in vivo. Use of the macrolactam BAF complex modulating compounds represent a method of HIV latency reversal with a unique mechanism of action, which can be optionally combined with other Latency Reversal Agents to improve reservoir targeting. The subject methods can be utilized in conjunction with any convenient methods of treating HIV or HIV latency, including methods related to immune system activation, antiretroviral therapies and / or anti-HIV agents.

Disclosed is an extracellular matrix genetranscription inhibitor composition or the like characterized by containing a cinnamoyl compound represented by the formula (I) below:and an inert carrier.

The present invention provides substituted pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives of formula (I), which have therapeutic Efficacy, especially as a selective transcriptional CDK inhibitor, including CDK7, CDK9, CDK12, CDK13 and CDK18 inhibitors, especially represented by transcriptional CDK7 inhibitors, where X, ring A, ring B, L 1 , L 2 , R 1 , R 2 , R 3 , R 4 , R 6 , m, n and p have the meanings given in the description, and the pharmaceutically acceptable salts of the compound of formula (I) can be used for treating and preventing diseases or conditions related to selective transcription of CDK suffered by mammals. The present invention also illustrates how to prepare compounds comprising at least one substituted pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[1,5-a]pyrimidine derivatives of formula (I) Compounds and pharmaceutical preparations of substances or pharmaceutically acceptable salts or stereoisomers thereof.

The invention discloses an application of epoxydaucenal A and B in hematopoietic stem cell aging resistance. Hematopoietic stem cells undergo self-renewal, differentiation, aging, death and other complex processes to maintain the generation of blood cells all one's life; and the maintenance of basic components of the hematopoietic system of a body and the gradual reduction of the functions and thequantity of hematopoietic stem cells in the aging process lead to the hematopoiesis function reduction and the immune function decline of the body. It is found in the invention that the epoxydaucenalA, the epoxydaucenal B, roseolic acid A or roseolic acid D can inhibiting p16 gene transcription in order to resist hematopoietic stem cell aging, and the epoxydaucenal A, the epoxydaucenal B, the roseolic acid A or the roseolic acid D can be processed to prepare a p16 gene transcription inhibitor and a drug for resisting hematopoietic stem cell aging.

The invention discloses a high-throughput screening method for screening a collagen transcription inhibitor for treating organ fibrosis. The method is characterized by comprising the following steps: cloning human Col1A1, Col1A2 and Col3A1 promoter-2000-100 regions, independently or jointly inserting a pGL3-basic reporter gene vector, transforming DH5 alpha bacteria and extracting plasmids to obtain plasmids for transfection; respectively transfecting the obtained plasmids and internal reference pRL-TK plasmids into fibroblasts, and then adding TGF-beta 1 to activate the fibroblasts; or adding a TGF beta R inhibitor at the same time; and after activation, treating according to a luciferase reporter gene detection kit after activation, reading chemiluminescence data by a microplate reader, and obtaining plasmids sensitive to synthesis of collagen induced by TGF-beta1. The practicability of the screening method is verified by the above results. The invention also discloses application of the method in quantitative analysis of the efficacy of drugs for inhibiting transcription of type I / III collagen.

The present invention provides novel inhibitors of inflammation and methods for treating inflammation by using these inhibitors. More specifically, the present invention provides transcription inhibitors, i.e., peptide fragments derived from internal regions of the Cytomegalovirus (CMV) IE2 protein that can inhibit production of inflammatory cytokines, e.g., Interleukin 1 beta(IFN-1β) and the methods for treating inflammatory diseases and CMV infection and related disorders, by using the IE2 fragments. An pharmaceutical composition comprising the transcription inhibitor are also provided.

The invention provides application of poloxamer in improvement of reverse transcriptase efficiency or improvement of reverse transcriptase inhibitor tolerance, and an additive mixture prepared by taking poloxamer as a core component and used in a reverse transcription process. The additive mixture not only can improve reverse transcription products (about 8 times) of normal high-purity RNA samples, but also has stronger tolerance and higher cDNA yield for RNA samples of complex sources, such as FFPE RNA or RNA containing reverse transcription inhibitors such as formaldehyde, ethanol, guanidine hydrochloride, guanidine isothiocyanate, heparin, tannic acid, formamide and phenol. The reverse transcriptase additive combination can significantly improve the sensitivity and accuracy of complex source pathological sample detection on RT-qPCR detection and RNA NGS library building, and is very suitable for the field of rapid diagnosis of diseases.

The invention discloses a conditionally replicating adenovirus vector for virus replication regulated by a TetR-KRAB-mediated transcription inhibition type Tet-On system, adenovirus E1 region comprises the following components in the following connection sequence: 5'-CMV promoter, TetR-KRAB gene, promoter TRE3G-E1b Pro containing a tetracycline responsive element, EcoR I enzyme cutting site, E1B Delta 55KD protein-deleted adenovirus E1A-E1B19KD gene sequence, enzyme cutting site Spe I and mRNA transcription termination signal SV40polyA-3'; the CMV promoter expresses transcription inhibitor TetR-KRAB; a gene sequence inserted into the two enzyme cutting sites of the EcoR I and the Spe I is a gene fragment from adenovirus E1A translation initiation site to adenovirus E1B19KD protein termination codon, the promoter TRE3G-E1b Pro containing the tetracycline responsive element expresses adenovirus E1A gene, adenovirus E1B19KD gene is expressed by the own promoter of the adenovirus E1B19KD, and the packed adenovirus is named as Ad5-CMV-TetR-KRAB-TRE3G-E1bPro-Delta 55KD. Tests show that the virus can be loaded into mesenchymal stem cells for application in study of tumor therapy.

The invention discloses a detection method for inhibiting escherichia coli in-vitro transcriptional activity by a bacterial transcription inhibitor. The detection method comprises the following steps: preparing an escherichia coli in-vitro transcription pKK450-DNA template; the preparation method comprises the following steps: preparing a fluorescent molecular beacon M.B. By taking a pKK3535 plasmid as a template; preparing an escherichia coli in-vitro transcription system, and detecting the in-vitro transcription inhibition activity of the escherichia coli transcription inhibitor. Compared with the prior art, the activity of the bacterial transcription inhibitor can be accurately detected; besides, high-efficiency and rapid detection instruments such as a fluorescence microplate reader and a 96-well plate are adopted, so that a large number of to-be-detected samples can be detected at high flux, and the method has important application value for screening transcriptional inhibition drugs. On the basis of the method, the action mechanism of the antibacterial substance can be analyzed so as to determine the influence of the antibacterial substance on bacterial transcription.

Provided herein are methods of treating patients with a combination of a transcription inhibitor (e.g., a STAT3 inhibitor) and an immune checkpoint blockade therapy (e.g., anti-PD-1 therapy, anti-PD-L1 therapy, anti-CTLA-4 therapy). The patient may have a proliferative disease, such as cancer or psoriasis. The patient may have a pathogenic infection.

The invention discloses application of LLDT-8 ((5R)-5-hydroxytriptolide) to preparation of a drug for treating non-alcoholic fatty liver disease. According to the application, the LLDT-8 serving as anSCD-1 transcription inhibitor and / or a fatty acid beta oxidation related gene transcription activator contains PPAR[alpha], ACADL, ACADM, ACOX1 and CPT1A. The LLDT-8 can inhibit mRNA of SCD-1, thereby inhibiting desaturation of fatty acid and inhibiting lipid regeneration; and meanwhile, the LLDT-8 can increase mRNA of fatty acid beta oxidation related genes, so that beta oxidation of fatty acidis increased, the content of beta-hydroxybutyric acid in serum is increased, and finally, lipid accumulation in the liver is inhibited by inhibiting the lipid generation and promoting lipid oxygenolysis.

The invention discloses a high-throughput screening method for screening collagen transcription inhibitors for treating organ fibrosis. The pGL3-basic reporter gene vector is combined and inserted, and the plasmid for transfection is obtained by transforming DH5α bacteria and plasmid extraction; the obtained plasmid and the internal reference pRL-TK plasmid are respectively transfected into fibroblasts, and then TGF-β1 is added for activation; or at the same time TGFβR inhibitor was added; after activation, it was processed according to the luciferase reporter gene detection kit, the chemiluminescence data was read by a microplate reader, and a plasmid sensitive to TGF-β1-induced collagen synthesis was obtained. The above results confirmed this screening method practicability. Also disclosed is the application of the method in the quantitative analysis of the pharmacodynamics of drugs that inhibit I / III collagen transcription.

The invention discloses an application of roseolic acid D in anti-senescence of hematopoietic stem cells. Hematopoietic stem cells undergo complex processes such as self-renewal, differentiation, aging and death to maintain the production of lifelong hematopoietic cells. Although the basic components of hematopoietic system are maintained during aging, the function and quantity of hematopoietic stem cells decrease gradually, which leads to the decrease of hematopoietic function and the decline of immune function. The invention shows that, Epoxycarotenal A, Epoxycarotenal B, Rosin A or Rosin Dcan resist senescence of hematopoietic stem cells by inhibiting transcription of p16 gene. Epoxycarotenal A, Epoxycarotenal B, Rosin A or Rosin D can be made into p16 gene transcription inhibitor andanti-senescence drug of hematopoietic stem cells.