38 results about "Histone Acetyltransferases" patented technology

To provide a transcriptional regulator protein degradation-promoting composition that is capable of directly facilitating the induction of transcription regulator protein degradation and also capable of enhancing the degradation-inducing effect through the combined administration of multiple components, wherein the transcriptional regulator protein degradation-promoting composition serves as a highly effective cancer therapeutic agent, as well as to provide a therapeutic agent comprising the same.SOLUTION: The present invention provides a transcriptional regulator protein degradation-promoting composition that facilitates the degradation of the transcription regulator protein, comprising a PARG inhibitor, a PERK inhibitor, an HSP90 inhibitor, or a histone acetylation enzyme inhibitor, as well as a therapeutic agent comprising the same.SELECTED DRAWING: None

The invention relates to an application of a histone H3K18 lactic acid modification related target in preparation of a medicine for preventing or treating atherosclerosis. The invention belongs to the field of biological medicine, and discloses histone acetyltransferase P300 and application of histone H3K18 lactylation (H3K18la) modification mediated by the histone acetyltransferase P300 as a new target spot for treating atherosclerosis (AS). Researches find that in the AS process, lactic acid accumulation in vascular smooth muscle cells (VSMCs) up-regulates H3K18la through P300 catalysis, and then the pathological phenotype of the VSMCs is induced, and plaque development is promoted. H3K18la can be reduced and the phenotype can be improved by inhibiting LDHA and MCT1 in vitro or knocking out a P300 gene; the P300 for in-vivo targeted inhibition of the VSMCs can significantly reduce the artery plaque. Therefore, the P300 and H3K18la inhibitors can be used for preparing the anti-atherosclerosis medicine.

Small molecules compounds and methods of their synthesis are provided. Small molecules identified can inhibit histone acetyltransferase 1 activity. Formulations and medicaments are also provided that are directed to the treatment of human disorders and conditions, such as, for example, neoplasms, cancers, viral, fungal, and parasitic infections, and aging. Therapeutics are also provided containing a therapeutically effective dose of one or more small molecule compounds, present either as pharmaceutically effective salt or in pure form, including, but not limited to, formulations for oral, intravenous, or intramuscular administration.

The invention concerns compositions and a method for treating or delaying the onset, progression, or relapse of a cancer in a subject, the method comprising administering, optionally with radiation therapy, an inhibitor of: (a) DNA-Dependent Protein Kinase catalytic subunit, and an inhibitor of Poly-ADP Ribose Polymerase, wherein the cancer has a histone H3.3 mutation or is a homologous recombination-defective (HR-defective) cancer; or (b) wild-type isocitrate dehydrogenase, wherein the IDH inhibitor is administered in an effective amount to decrease wild-type IDH activity in cells of the cancer, and wherein the cancer carries a histone H3.3 K27M mutation, and / or the cancer has low DNA methylation and / or low histone methylation; or (c) histone acetyltransferase, wherein the cancer carries a histone H3.3 K27M mutation, and / or high histone acetylation; or (d) histone deacetylase, wherein the cancer carries a histone H3.3 K27M mutation, and / or has high histone acetylation; or (e) any combination thereof.

The invention discloses application of a histone acetyltransferase inhibitor in preparation of a medicine for improving liver fatty degeneration. The invention discloses application of a histone acetyltransferase inhibitor for selectively inhibiting Gcn5 acetylation of histone H3 in preparation of drugs for treating and / or preventing diseases caused by liver fatty degeneration. And the histone acetyltransferase inhibitor for selectively inhibiting acetylation of Gcn5 on histone H3 is CPTH2. The compound CPTH2 reduces the protein abundance of a liver lipid synthesis transcription factor SREBP1c by inhibiting the acetylation activity of H3K9 and H3K14, and obviously improves the liver fatty degeneration of C57BL / 6J mice fed with high fat diet.

Compounds and compositions comprising compounds that modulate histone acyltransferase (HAT). Methods of treating neurodegenerative disorders, conditions associated with amyloid-beta peptide deposit accumulation, Tau protein levels, and / or alpha-synuclein accumulation, and cancer by administering to a subject a compound that modulates HAT.

The present invention is a preparation and application of a histone acetyltransferase electrochemical sensor based on a "Cu(II) to Cu(II)" mechanism. First, the sulfhydryl group in CoA and Cu(II) generate a CoA-Cu(II) complex in situ, which can be regarded as a nanochain complex with multiple adenines as side groups. The complex can be combined with GO through its adenine side group through a π-π conjugation effect, so as to be combined and fixed on the electrode surface, and the voltage signal of Cu(II) is collected by FSCV technology. Because the polymerization of CoA and Cu(II) can realize the electrochemical sensing analysis of CoA, and because CoA is the product of the HAT catalytic reaction, the electrochemical sensing analysis of HAT can be realized. By changing the concentration of CoA or HAT, a series of FSCV signal sizes corresponding to CoA and HAT at different concentrations can be obtained; when the inhibitor anacardic acid / C646 is added, the HAT activity is inhibited, CoA cannot be generated, and the complex cannot be formed, thereby realizing the screening of HAT inhibitors. Based on this, a fast, simple, reliable, stable and highly sensitive FSCV analysis method is constructed.

The invention belongs to the technical field of biological medicines, and particularly discloses application of a KAT6A inhibitor in preparation of a medicine for treating diabetic cardiomyopathy. Specifically, the invention relates to an application of a histone acetyltransferase inhibitor in preparation of drugs for treating or preventing diabetic cardiomyopathy. The invention discloses an application of a KAT6A inhibitor in preparation of a medicine for treating diabetic cardiomyopathy, which is used for treating or preventing diabetic cardiomyopathy by inhibiting acetylation modification of dihydrolipoamide transacetylase protein and inhibiting cell copper death.

Provided are a compound defined by chemical formula 1, a stereoisomer thereof, a tautomer thereof, and a pharmaceutically acceptable salt thereof. In chemical formula 1, R is a site which binds to a histone acetyl transferase region of EP300. The compound of the present invention can reduce the intracellular level of EP300. [Chemical formula 1]

Cell culture media comprising luteinizing hormone, follicle-stimulating hormone and at least one histone acetyltransferase inhibitor or reverse transcriptase inhibitor are provided. Methods of in vitro maturing a human oocyte, determining suitability for in vitro maturation, as well as kits comprising media, luteinizing hormone, follicle-stimulating hormone and at least one histone acetyltransferase inhibitor or reverse transcriptase inhibitor are also provided.

The invention relates to an inhibitor of a histone acetyl transferase (HAT) activity of CREBBP(CBP) / p300 for use in the treatment of cytopenia. In embodiments, the inhibitor preferably suppresses a HAT domain of CBP / p300, more preferably by competing with acetyl CoA for binding to the HAT domain, thereby suppressing HAT enzymatic activity. In embodiments, the inhibitor induces acute and / or transient leukocytosis comprising mobilization of leukocytes from the bone marrow into the blood of a subject. The invention further relates to a pharmaceutical composition for use in the treatment of cytopenia, comprising the inhibitor according to the invention, and to a combination medication for use in the treatment of cytopenia, comprising the inhibitor according to the invention and a G-CSF or derivative thereof, preferably compound selected from G-CSF, recombinant G-CSF and / or G-CSF analogues.

The disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.

To provide a novel therapeutic or prophylactic agent for abnormal angiogenesis and its applications.SOLUTION: A therapeutic or prophylactic agent for abnormal angiogenesis is used that contains a histone acetyltransferase inhibitor as an active ingredient.SELECTED DRAWING: None

The invention provides pharmaceutical compositions and methods for treating cancer, neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and / or accumulations of alpha-synuclein by administering a HAT modulator and a HDAC modulator to a subject.

The invention discloses a diagnostic marker for the drug resistance of kidney cancer sunitinib. The diagnostic marker for the drug resistance of kidney cancer sunitinib is selected from a group consisting of histone acetyltransferase KAT2A. The invention further discloses a kit for detecting the sunitinib drug resistance of the kidney cancer. The kit comprises a reagent for detecting the expression quantity of KAT2A. The KAT2A provided by the invention is used as a renal cancer sunitinib drug resistance diagnosis marker, has good specificity and high sensitivity, provides a new diagnosis and treatment means for renal cancer sunitinib drug resistance, is beneficial to drug resistance monitoring and avoids further invalid treatment, and has a good medical conversion prospect.

Compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). Methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and / or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.

Cell culture media comprising luteinizing hormone, follicle-stimulating hormone and at least one histone acetyltransferase inhibitor or reverse transcriptase inhibitor are provided. Methods of in vitro maturing a human oocyte, determining suitability for in vitro maturation, as well as kits comprising media, luteinizing hormone, follicle-stimulating hormone and at least one histone acetyltransferase inhibitor or reverse transcriptase inhibitor are also provided.

The invention provides a diagnostic reagent for lung adenocarcinoma radiotherapy prognosis, which comprises a reagent for detecting the expression level of histone acetyltransferase 1 (HAT1) and / or a reagent for detecting the lactylation level of replication protein A1 (Replication Protein A1, RPA1). The invention also provides application of the diagnostic reagent. The invention provides application of HAT1-mediated RAP1 protein lactylation modification to evaluation of radiotherapy resistance characteristics of lung adenocarcinoma patients and a targeting strategy, and provides more diversified and personalized means for LUAD clinical diagnosis and treatment.

Addressing the challenges of low genome editing efficiency and low efficiency in producing plants with mutations introduced into target genes, this research aims to provide plant genome editing technology with higher genome editing efficiency. [Solution] A method for producing genome-edited plants, comprising introducing a histone acetyltransferase expression cassette and a site-specific nuclease expression cassette into a plant.

Disclosed is a method of treating diffuse midline glioma (DMG), such as diffuse intrinsic pontine glioma (DIPG), with a compound that possesses inhibitory activity against histone acetyltransferase p300 (EP300) and CREB-binding protein (CBP).

The disclosure, in one aspect, relates to methods for treating cancer in a subject, the methods including at least the steps of administering at least one drug from each of at least two classes selected from an inhibitor of poly-ADP ribose polymerase (PARP inhibitor), an inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs inhibitor), an inhibitor of wild-type isocitrate dehydrogenase (IDH inhibitor), an inhibitor of histone acetyltransferase (HAT inhibitor), an inhibitor of histone deacetylase (HDAC inhibitor), an inhibitor of DNA polymerase Θ (POLΘ inhibitor), an inhibitor of platelet-derived growth factor receptor (PDGFR inhibitor), and a DNA alkylating agent to the subject. In any of these aspects, the disclosed method allows for administering lower doses of the drugs in combination compared to administration as single drugs while preventing the recurrence of the cancer, preventing drug resistance of the cancer, and reducing side effects associated with cancer treatment.

The invention belongs to the technical field of biological medicines, and relates to a histone acetyltransferase p300 / CBP degradation compound. The invention specifically relates to a histone acetyltransferase p300 / CBP degradation compound with a structure as shown in a formula (P-L-D (I)) or derivatives (including stereoisomers, deuterated compounds, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or co-crystals) of the histone acetyltransferase p300 / CBP degradation compound. The invention also relates to a medicinal composition of the compound or the derivative thereof and application of the compound or the derivative thereof in preparation of medicines for treating p300 / CBP related diseases. The compound comprises a part combined with histone acetyltransferase p300 / CBP and a part combined with E3 ubiquitin ligase, can be combined with and degrade p300 / CBP protein in tumor cells, and has a remarkable inhibition effect on growth of the tumor cells.

Provided are compounds of Formula (I):and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of conditions associated with histone acetyltransferase (HAT).

The application belongs to the technical field of biological medicine, and provides application of a peptide in a histone acetyltransferase MOF biological activity inhibitor, and an amino acid sequence of the peptide is PYQRRGYGKF, as shown in SEQ ID No. 1. The application finds a biological activity domain of the histone acetyltransferase MOF, identifies an amino acid sequence capable of inhibiting the biological activity of the MOF, and proves that the sequence small molecule peptide can play a role in inhibiting the biological function and acetylation catalytic activity of the MOF, and can be applied as the MOF inhibitor to alleviate or treat diseases caused by the increase of the biological activity of the MOF.

Methods to identify modulators of histone acetyltransferases are described. Modulators of histone acetyltransferases can be used to treat individuals. In some instances, modulators of histone acetyltransferases are utilized to treat individuals having a neoplasm.

Disclosed is a histone acetyltransferase (HAT) inhibitor. Provided are a compound represented by the general formula I, a pharmaceutically acceptable salt, a stereoisomer, an enantiomer, a diastereoisomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method therefor, a pharmaceutical composition comprising same and use thereof in the treatment of various HAT-related diseases or conditions.

The invention discloses application of SIRT7 serving as a target in screening of reagents or drugs for inhibiting HBV replication and screening of drugs for treating hepatitis B. The invention also discloses application of the histone acetyltransferase inhibitor in preparation of a reagent or a medicine for inhibiting HBV replication and in preparation of a medicine for treating hepatitis B. The research finds that histone acetylation can promote HBV expression, SIRT7 can inhibit HBV replication through deacetylation of histone H3K18Ac, and H3K18Ac can be used as an important target for HBV treatment; the histone acetyltransferase specific inhibitor inhibits H3K18 acetylation on ccc-DNA, further inhibits HBV replication, is expected to serve as a new medicine for inhibiting HBV replication, and provides a new direction and thought for treatment of HBV.

The invention provides application of histone acetyltransferase GhGCN5 in regulation and control of cotton fiber development, and relates to the technical field of molecular breeding. After the GhGCN5 gene is edited in cotton, both the initial number of fibers and the length of mature fibers are increased; the overexpression GhGCN5 gene can significantly inhibit the growth of cotton fibers in the initial and elongation stages, and leads to the reduction of the length and quantity of mature fibers. The GhGCN5 gene capable of regulating and controlling the development of the cotton fibers, provided by the invention, provides new gene resources and theoretical support for the quality improvement of the cotton fibers.

To provide a prophylactic and / or therapeutic agent for a skin disorder associated with a histone deacetylase 4 abnormality.SOLUTION: The present invention provides a prophylactic and / or therapeutic agent for a skin disorder associated with a histone deacetylase 4 abnormality, comprising a histone acetyltransferase inhibitor as an active ingredient. This prophylactic and / or therapeutic agent makes it possible to prevent and / or treat a skin disorder associated with a histone deacetylase 4 abnormality.SELECTED DRAWING: Figure 18